BACKGROUND Smoking is a leading cause of carcinogenesis in the head and neck region,representing a critical public health issue.Identifying genotoxic damage in smokers can provide valuable insights for developing prev...BACKGROUND Smoking is a leading cause of carcinogenesis in the head and neck region,representing a critical public health issue.Identifying genotoxic damage in smokers can provide valuable insights for developing preventive interventions.AIM To assess genotoxic damage through the micronucleus assay in exfoliated buccal mucosa cells from users of conventional tobacco,reverse smoking,cannabis,electronic cigarettes,and non-smokers.METHODS A cross-sectional study was conducted with 100 participants divided into five groups:20 conventional tobacco smokers,20 reverse smokers,20 electronic cigarette users,20 cannabis users,and 20 non-smokers.Exfoliated buccal mucosa cells were analyzed using Giemsa and Papanicolaou staining to identify micronuclei(MN)as markers of genotoxic damage.RESULTS MN were present in 86%of the samples.Statistically significant differences were observed in the median micronucleus count between conventional,reverse,and electronic cigarette smokers compared to non-smokers(P<0.001),while no significant difference was found for cannabis smokers(P=0.89).A significant correlation was identified between the presence of oral lesions and micronucleus count(P=0.03).Regression analysis ruled out alcohol as a confounding factor.CONCLUSION This study identified genotoxic damage associated with various smoking habits,except for cannabis use,highlighting the need for public health interventions to reduce smoking and mitigate its genotoxic effects.These findings provide a foundation for future research and the implementation of preventive policies.展开更多
Pimpinella anisum,commonly known as anise,is generally used in both folk medicine and the culinary world.In traditional medicine,it is valued for its digestive,respiratory,and antispasmodic properties.This study aims ...Pimpinella anisum,commonly known as anise,is generally used in both folk medicine and the culinary world.In traditional medicine,it is valued for its digestive,respiratory,and antispasmodic properties.This study aims to examine the volatile compounds and antibacterial effect of P.anisum essential oil(PAEO)as well as for the first time its genotoxicity employing both in vitro and computational approaches.Gas chromatography-mass spectrometry(GC-MS)analysis identified anethole as the principal compound,which comprises 92.47%of PAEO.PAEO was tested for its potential antibacterial properties against Bacillus subtilis ATCC 6633,Listeria innocua ATCC 33090,Staphylococcus aureus ATCC 29213,Klebsiella aerogenes ATCC 13048,and a clinical strain of Salmonella enterica serotype Typhi.PAEO displayed noteworthy antibacterial action toward all tested bacteria,especially Staphylococcus aureus,with an inhibition zone of 21.43±0.87 mm,as determined by the disc-diffusion test.Varied between 0.0625%and 2%v/v,while the MBC values ranged from 0.125%to 8%v/v,reflecting the strength of the tested EO.The MBC/MIC ratios indicated the bactericidal nature of PAEO.The results of molecular docking revealed strong binding interactions between key PAEO molecules and microbial target proteins.ADMET(Absorption,Distribution,Metabolism,Excretion,and Toxicity)analysis confirmed favorable pharmacokinetic properties,indicating its potential as a safe therapeutic agent.Additionally,genotoxicity was assessed using the comet assay,which demonstrated minimal genotoxic risk,affirming the oil’s safety.These results highlight the promising antimicrobial properties of PAEO and its possible use as an active agent in the pharmacy,food,and cosmetic sectors.展开更多
Synthesis of zinc oxide nanoparticles(ZnO-NPs)via green method is an outstanding alternative to conventional/regular methods;however,the safety or toxicity of the biosynthesized ZnO-NPs in vivo is not fully explored.T...Synthesis of zinc oxide nanoparticles(ZnO-NPs)via green method is an outstanding alternative to conventional/regular methods;however,the safety or toxicity of the biosynthesized ZnO-NPs in vivo is not fully explored.This study was conducted to evaluate the protective efficiency of cinnamaldehyde-loaded chitosan nanoparticles(Cin@CSNPs)against oxidative damage and genotoxicity of ZnO-NPs in mice.ZnO-NPs were biosynthesized using the extract of fresh leaves of Mentha pulegium L.Cin was extracted from cinnamon essential oil,and was loaded into chitosan nanoparticle(Cin@CSNPs).Both ZnO-NPs,Cin@CSNPs and CSNPs were characterized.The in vitro release of Cin@CSNPs was determined.In the biological study,6 groups of male BALB/c mice were treated by gavage for 3 weeks as follows,control group,the group received ZnO-NPs(25 mg/kg b.w),the groups received Cin@CSNPs at low dose(50 mg/kg b.w)or high dose(100 mg/kg b.w),and the groups received ZnO-NPs plus Cin@CSNPs at the 2 tested doses.Blood and tissue samples were collected for different biochemical,genetical and histological studies.The particle size of ZnO-NPs,CSNPs,and Cin@CSNPs were(20.78±2.60),(170.0±3.7),and(218.23±2.90)nm,andξ-potential were(32.7±4.6),(8.32±0.27)and(4.80±0.21)mV,respectively.ZnO-NPs disturbed the biochemical and oxidative stress indices,AFP,CEA,TNF-α,chromosomal aberrations in somatic and germ cells,and sperm abnormality along with severe pathological changes in the hepatic,renal,and testicular tissues.Cin@CSNPs improved significantly all the parameters tested and the histological picture in a dose-dependent.Therefore,the biosynthesized ZnO-NPs exhibit oxidative damage and genotoxicity,and Cin@CSNPs have potential protective effects against the risks of ZnO-NPs and may be a promising tool to overcome the challenges of using Cin in food and pharmaceuticals applications.展开更多
To further assess hyperoside as a potential new anti-hepatitis B virus （HBV） drug, the safety of hyperoside extracted from Abelmoschus manihot （L.） Medic was evaluated by testing its acute toxicity and mutagenic r...To further assess hyperoside as a potential new anti-hepatitis B virus （HBV） drug, the safety of hyperoside extracted from Abelmoschus manihot （L.） Medic was evaluated by testing its acute toxicity and mutagenic risk. To test the acute toxicity of hyperoside, we determined the median lethal dose （LD 50 ） in mice. Forty healthy BALB/c mice （20 per sex） were administered a single oral dose of 5000 mg/kg hyperoside via the intragastrical route. The number of animals poisoned and died was noted daily for 14 consecutive days. All animals survived and appeared active and normal, indicating that the LD 50 of hyperoside was more than 5000 mg/kg. Potential genotoxicity of hyperoside was investigated using a bacterial reverse mutation assay （Ames test）, a chromosome aberration test in Chinese hamster lung （CHL） fibroblasts, and an in vivo micronucleus test in rat bone marrow cells. In the bacterial reverse mutation assay, we observed no increases in the number of revertant colonies at any concentrations of hyperoside regardless of metabolic activation （S9） in all tester strains （TA97, TA98, TA100 and TA102） compared to the vehicle control （P0.05）. Hyperoside did not cause significant structural aberration in CHL cells in the presence or absence of S9 （P0.05）. The micronuclei rates of mice bone marrow cell in all groups showed no significant difference when compared with the negative control （P0.05）. In summary, hyperoside showed no genotoxicity in our experimental conditions.展开更多
Objective:To identify the available phytochemicals and carotenoids in the selected green algae and evaluate the potential genotoxic/antigenotoxic effect using lymphocytes.Methods:Organic,solvent extracts of Chlorococc...Objective:To identify the available phytochemicals and carotenoids in the selected green algae and evaluate the potential genotoxic/antigenotoxic effect using lymphocytes.Methods:Organic,solvent extracts of Chlorococcum humicola(C.humicola)were used for the phytochemical analysis.The available carotenoids were assessed by HPLC,and LC-MS analysis.The genotoxicity was induced by the benzo(a)pyrene in the lymphocyte culture,the genotoxic and antigenotoxic effects of algal carotenoids with and without genotoxic inducer were evaluated by chromosomal aberration(CA),sister chromatid exchange(SCE)and micronucleus assay(MN).Results:The results of the analysis showed that the algae were rich in carotenoids and fatty acids.In the total carotenoids lutein,β-carotene andα-carotene were found to be present in higher concentration.The frequency of CA and SCE increased by benzo(a)pyrene were significantly decreased by the carotenoids(P<0.05 for CA,P<0.001 for SCE).The MN frequencies of the cells were significantly decreased by the treatment with carotenoids when compared with the positive controls(P<0.05).Conclusions:The findings of the present study demonstrate that,the green algae C.humicola is a rich source of bioactive compounds especially carotenoids which effectively fight against environmental genotoxic agents,the carotenoids itself is not a genotoxic substance and should be further considered for its beneficial effects.展开更多
Adsorbable organic halogens（AOX） are a general indicator for the total amount of compounds containing organically bonded halogens. AOX concentrations and components were investigated along the wastewater treatment p...Adsorbable organic halogens（AOX） are a general indicator for the total amount of compounds containing organically bonded halogens. AOX concentrations and components were investigated along the wastewater treatment process in four large-scale pharmaceutical factories of China, and genotoxicity based on the SOS/umu test was also evaluated. The results showed that AOX concentrations in wastewater of four factories ranged from 4.6 to 619.4 mg/L, which were high but greatly different owing to differences in the raw materials and products. The wastewater treatment process removed 50.0%–89.9% of AOX, leaving 1.3–302.5 mg/L AOX in the effluents. Genotoxicity levels ranged between 2.1 and 68.0 μg 4-NQO/L in the raw wastewater and decreased to 1.2–41.2 μg 4-NQO/L in the effluents of the wastewater treatment plants（WWTPs）. One of the main products of factory I, ciprofloxacin, was identified as the predominant contributor to its genotoxicity. However, for the other three factories, no significant relationship was observed between genotoxicity and detected AOX compounds.展开更多
Besides obvious benefits,the Three Gorges Dam＇s construction resulted in new pollution scenarios with the potentials to threaten the Three Gorges Reservoir（TGR） ecosystem.In order to record organic contamination,to...Besides obvious benefits,the Three Gorges Dam＇s construction resulted in new pollution scenarios with the potentials to threaten the Three Gorges Reservoir（TGR） ecosystem.In order to record organic contamination,to find links to ecotoxicological impacts and to serve as reference for ensuing monitoring,several sites in the TGR area were screened applying the triad approach with additional lines-of-evidence as a holistic assessment method.Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011 and 2012 to determine organic pollution levels,mutagenic potentials and genotoxic impacts.Two regional hot-spots near the cities of Chongqing and Kaixian were identified and further investigated in 2013.Only polycyclic aromatic hydrocarbons（PAHs） could be detected in sediments in 2011（165-1653 ng/g）,emphasizing their roles as key pollutants of the area.Their ubiquity was confirmed at Chongqing（150-433 ng/g） and Kaixian（127-590 ng/g） in2013.Concentrations were comparable to other major Chinese and German rivers.However,the immense sediment influx suggested a deposition of 216-636 kg PAH/day（0.2-0.6 mg PAH/（m2·day））,indicating an ecotoxicological risk.PAH source analysis highlighted primary impacts of combustion sources on the more industrialized upper TGR section,whereas petrogenic sources dominated the mid-low section.Furthermore,sediment extracts from several sites exhibited significant activities of frameshift promutagens in the Ames fluctuation assay.Additionally,significant genotoxic impairments in erythrocytes of P.vachellii were detected（Chongqing/Kaixian）,demonstrating the relevance of genotoxicity as animportant mode of action in the TGR＇s fish.PAHs,their derivatives and non-target compounds are considered as main causative agents.展开更多
The freshwater luminescent bacteria Vibrio-qinghaiensis sp.-Q67 test and the Vicia faba root tip test associated with solid-phase extraction were applied for cytotoxicity and genotoxicity assessment of organic substan...The freshwater luminescent bacteria Vibrio-qinghaiensis sp.-Q67 test and the Vicia faba root tip test associated with solid-phase extraction were applied for cytotoxicity and genotoxicity assessment of organic substances in three rivers, two lakes and effluent flows from two wastewater treatment plants （WWTPs） in Xi＇an, China. Although the most seriously polluted fiver with high chemical oxygen demand （COD） and total organic carbon （TOC） showed high cytotoxicity （expressed as TIIs0, the toxicity impact index） and genotoxicity （expressed as RMCN, the relative frequency of micronucleus）, no correlative relation was found between the ecotoxicity and organic content of the water samples. However, there was a linear correlative relation between TIIs0 and RMCN for most water samples except that from the Zaohe River, which receives discharge from WWTP and untreated industrial wastewaters. The ecotoxicity of the organic toxicants in the Chanhe River and Zaohe River indicated that cytotoxic and genotoxic effects were related to the pollutant source. The TII50 and RMCN were also found to correlate roughly to the dissolved oxygen concentration of the water. Sufficient dissolved oxygen in surface water is thus proved to be an indicator of a healthy water environmental condition.展开更多
An increasing number of industrial, agricultural, and commercial chemicals in the aquatic environment leads to various deleterious effects on organisms, which is becoming an increasingly serious problem in China. In t...An increasing number of industrial, agricultural, and commercial chemicals in the aquatic environment leads to various deleterious effects on organisms, which is becoming an increasingly serious problem in China. In this study, the comet assay was conducted to investigate the genotoxicity to human body caused by organic concentrates in the drinking water sources of Nanjing City from Yangtze River of China, and health and ecology risk due to expose to these organic pollutants were evaluated with the multimedia environmental assessment system （MEAS）. For all the water samples, they were collected from four different locations in the drinking water sourcr samples, es of Nanjing City. The results of the comet assay showed that all the organic concentrates from the water samples could induce different levels DNA damages on human peripheral blood lymphocytes, and a statistically significant difference （p〈0.01） was observed compared with the solvent control, which demonstrated the genotoxicity was in existence. According to the ambient severity （AS） of individual compound, we had sorted out the main organic pollutants in the drinking water source of the four waterworks, and the results showed that there was some potential hazard to human body for all the source water, namely the total ambient severity （TAS） of health for each water source was more than 1. However, the TAS of ecology for each water source was less than 1, which indicated that it was safe to ecology. The results of this investigation demonstrate the application of the comet assay and the MEAS in aquatic environmental monitoring studies, and the comet assay found to be fast, sensitive, and suitable for genotoxicity monitoring programs of drinking water source.展开更多
The disinfection of drinking water is an important public health service that generates high quality, safe and palatable tap water. The disinfection of drinking water to reduce waterborne disease was an outstanding pu...The disinfection of drinking water is an important public health service that generates high quality, safe and palatable tap water. The disinfection of drinking water to reduce waterborne disease was an outstanding public health achievement of the 20 th century.An unintended consequence is the reaction of disinfectants with natural organic matter,anthropogenic contaminants and bromide/iodide to form disinfection by-products（DBPs）.A large number of DBPs are cytotoxic, neurotoxic, mutagenic, genotoxic, carcinogenic and teratogenic. Epidemiological studies demonstrated low but significant associations between disinfected drinking water and adverse health effects. The distribution of DBPs in disinfected waters has been well defined by advances in high precision analytical chemistry. Progress in the analytical biology and toxicology of DBPs has been forthcoming.The objective of this review was to provide a detailed presentation of the methodology for the quantitative, comparative analyses on the induction of cytotoxicity and genotoxicity of103 DBPs using an identical analytical biological platform and endpoints. A single Chinese hamster ovary cell line was employed in the assays. The data presented are derived from papers published in the literature as well as additional new data and represent the largest direct quantitative comparison on the toxic potency of both regulated and emerging DBPs.These data may form the foundation of novel research to define the major forcing agents of DBP-mediated toxicity in disinfected water and may play an important role in achieving the goal of making safe drinking water better.展开更多
The effects of ozonation on the formation potential of typical disinfection byproducts （DBPs） and the changes of genotoxicity during post chlorination of tertiary effluent from a sewage treatment plant were investig...The effects of ozonation on the formation potential of typical disinfection byproducts （DBPs） and the changes of genotoxicity during post chlorination of tertiary effluent from a sewage treatment plant were investigated. Ozonation enhanced the yields of all detected chlorine DBPs except CHCI3. At a chlorine dose of 5 mg/L, the three brominated THMs and five HAAs increased, while chloroform decreased with the increase of ozone dose from 0 to 10 mg/L （ozone dose in consumption base）. At a chlorine dose of 10 mg/L, the two mixed bromochloro species THMs and two dominant HAAs （DCAA and TCAA） increased firstly and then decreased with the increase of ozone dose, with the turning point approximately occurring at an ozone dose of 5 mg/L. The genotoxicity detected using umu test, on the other hand, was removed from 7 Ixg 4-NQO/L to a negligible level by ozonation under an ozone dose of 5 mg/L. Chlorination could further remove the genotoxicity to some extent. It was found that SUVA （UV absorbance divided by DOC concentration） might be used as an indicative parameter for monitoring the removal of genotoxicity during the oxidation.展开更多
Objective: To assess and compare the cytotoxic, genotoxic, apoptotic and reactive oxygen species(ROS) generating effects of naringenin(NG) and its new derived compound naringenin-oxime(NG-Ox) on MCF-7, HT-29, PC-12 ca...Objective: To assess and compare the cytotoxic, genotoxic, apoptotic and reactive oxygen species(ROS) generating effects of naringenin(NG) and its new derived compound naringenin-oxime(NG-Ox) on MCF-7, HT-29, PC-12 cancer and L-929 normal cell lines.Methods: The cells were incubated with different doses of NG-Ox and NG(50–1 000 mmol/L) for 24 h. The cell viability was assessed based on ATP cell viability assay.Intracellular accumulation of ROS was determined using the fluorescent probes 2070-dichlorodihydrofluorescin diacetate. Genotoxic effects were evaluated by alkaline single cell gel electrophoresis assay(comet assay) and, the apoptotic effect was evaluated by acridine orange staining at below the IC50 levels.Results: Both NG-Ox and NG exhibited cytotoxic, genotoxic and apoptotic effects and resulted in increased ROS values in a dose-dependent manner. The effects were more pronounced on cancer cell lines. The cytotoxic, genotoxic and apoptotic effects of NG-Ox were higher than that of NG in all cell lines. Significant correlations were observed between cell viability, DNA damage, apoptosis and ROS, in all cell lines exposed to either NG-Ox or NG.Conclusions: This study showed that both NG-Ox and NG possess cytotoxic, genotoxic and apoptotic activities through the production of ROS on cells, NG-Ox being the more effective one. Therefore, derived compound of NG might be used as antiproliferative agents for the treatment of cancer.展开更多
The following experiments were conducted to evaluate the genotoxic effects of GMA (glycidyl methacrylale) on mammalian and human cells.(1) Using the absorption spectrum shift method in vitro, we observed that the maxi...The following experiments were conducted to evaluate the genotoxic effects of GMA (glycidyl methacrylale) on mammalian and human cells.(1) Using the absorption spectrum shift method in vitro, we observed that the maximums of calf thymus DNA and GMA were shifted toward longer wavelengths (a change of more than 15nm) and the absorbance decreased after incubation at room temperature for 15min or more.The result indicates that binding of DNA and GMA had occurred.The binding force is strong, not affected by the addition of concentrated sodium chloride solution, and only slightly decreased by the addition of 8 M urea solution.Therefore the bond between DNA and GMA might be covalent.(2) In cell cultures, unscheduled DNA synthesis (UDS) in human and/or rat lymphocyte was induced and DNA semiconserva-tive replication was inhibited by GMA at concentrations of less than 5.2 mM.(3) Sperm abnormality tests and assays of UDS in germ cells of male mice were conducted to study the in vivo genotoxicity of GMA.The results revealed that GMA could damage DNA, increase sperm abnormality frequency, and reduce the number of sperm cells, 1990 Academic Press.Inc.展开更多
Lichens are widely used in biomonitoring studies of air pollution, either as bioindicators of air quality or as bioaccumulators of atmospheric deposition. Over the past decade, several molecular techniques have been d...Lichens are widely used in biomonitoring studies of air pollution, either as bioindicators of air quality or as bioaccumulators of atmospheric deposition. Over the past decade, several molecular techniques have been developed to provide information on diversity, genotoxicology, genetic relationships, etc. The heavy metal contents of Evernia prunastri samples were determined by atomic absorption spectrometry. The Random Amplified Polymorphic DNA Polymerase Chain Reaction （RAPD-PCR） method was used to describe the pattern of DNA band variation in the samples influenced by the environmental pollution. The study was designed to describe the level of pollution in an area contaminated with smoke and waste from an iron-steel factory, and to reveal the level of potential genotoxic agents around this source of pollution. The study also examined the suitability of the lichen samples for the detection of genotoxicity.展开更多
Objective:To evaluate the cytotoxicity and genotoxicity activity of Euphorbia hirta(E.hirta)in MCF-7 cell line model using comet assay.Methods:The cytotoxicity of E.hirta extract was investigated by employing brine sh...Objective:To evaluate the cytotoxicity and genotoxicity activity of Euphorbia hirta(E.hirta)in MCF-7 cell line model using comet assay.Methods:The cytotoxicity of E.hirta extract was investigated by employing brine shrimp lethality assay and the genotoxicity of E.hirta was assessed by using Comet assay.Results:Both toxicity tests exhibited significant toxicity result.In the comet assay,the E.hirta extract exhibited genotoxicity effects against MCF-7 DNA in a time-dependent manner by increasing mean percentage of DNA damage.The extract of E.hirta showed significant toxicity against brine shrimp with an LC_(50)value of 620.382μg/mL(24 h).Comparison with positive control potassium dichroniate signifies that cytotoxicity exhibited by the methanol extract might have moderate activity.Conclusion:The present work confirmed the cytotoxicity and genotoxicity of E.hirta.However,the observed toxicity of E.hta extracts needs to be confirmed in additional studies.展开更多
Objective Many studies have been conducted in order to evaluate the genotoxicity of chemicals and waste materials, which utilized in vivo test protocols. The use of animals for routine toxicity testing is now question...Objective Many studies have been conducted in order to evaluate the genotoxicity of chemicals and waste materials, which utilized in vivo test protocols. The use of animals for routine toxicity testing is now questioned by a growing segment of society. Methods Keeping the above fact in mind, we have conducted in the present study the genotoxicity evaluation of oily sludge samples generated from a petroleum refinery and petrochemical industry and ETP sludge from petroleum refinery using DNA damage, chromosomal aberration, p53 protein induction and apoptosis in short term in vitro mammalian Chinese Hamster Ovary cell cultures. Results It is evident from the results that the oily sludge compounds derived from petroleum refinery and petrochemical industry could cause DNA damage, chromosomal aberration, p53 protein accumulation and apoptotic cell death on exposure to oily sludge extracts in the presence of metabolic activation system (S-9 mix), however, ETP sludge extract could not cause significant genotoxicity in comparison to oily sludge extract and negative control. Conclusion The effect may be attributed to polycyclic aromatic hydrocarbons present in the samples as evidenced from GC-MS.展开更多
Covalent organic nanospheres(CONs)were explored as a fiber coating for solid-phase microextraction of genotoxic impurities(GTIs)from active ingredients(AIs).CONs were synthesized by an easy solutionphase procedure at...Covalent organic nanospheres(CONs)were explored as a fiber coating for solid-phase microextraction of genotoxic impurities(GTIs)from active ingredients(AIs).CONs were synthesized by an easy solutionphase procedure at 25℃.The obtained nanospheres exhibited a high specific surface area,good thermostability,high acid and alkali resistance,and favorable crystallinity and porosity.Two types of GTIs,alkyl halides(1-iodooctane,1-chlorobenzene,1-bromododecane,1,2-dichlorobenzene,1-bromooctane,1-chlorohexane,and 1,8-dibromooctane)and sulfonate esters(methyl p-toluenesulfonate and ethyl ptoluenesulfonate),were chosen as target molecules for assessing the performance of the coating.The prepared coating achieved high enhancement factors(5097-9799)for the selected GTIs.The strong affinity between CONs and GTIs was tentatively attributed to π-π and hydrophobicity interactions,large surface area of the CONs,and size-matching of the materials.Combined with gas chromatography-mass spectrometry(GC-MS),the established analytical method detected the GTIs in capecitabine and imatinib mesylate samples over a wide linear range(0.2-200 ng/g)with a low detection limit(0.04-2.0 ng/g),satisfactory recovery(80.03%-109.5%),and high repeatability(6.20%-14.8%)and reproducibility(6.20%-14.1%).Therefore,the CON-coated fibers are promising alternatives for the sensitive detection of GTIs in AI samples.展开更多
Particulate matter in ambient air constitutes a complex mixture of fine and ultrafine particles composed of various chemical compounds including metals, ions, and organics. A multidisciplinary approach was developed b...Particulate matter in ambient air constitutes a complex mixture of fine and ultrafine particles composed of various chemical compounds including metals, ions, and organics. A multidisciplinary approach was developed by studying physico-chemical characteristics and mechanisms involved in the toxicity of particulate atmospheric pollution. PM0.3-2.s and PM2.5 including ultrafine particles were sampled in Dunkerque, a French industrialized seaside city. PM samples were characterized from a chemical and toxicological point of view. Physico-chemical characterization evidenced that PM2.5 comes from several sources： natural ones, such as soil resuspension and marine sea-salt emissions, as well as anthropogenic ones, such as shipping traffic, road traffic, and industrial activities. Human BEAS-2B tung cells were exposed to PM0.3-2.5, or to the Extractable Organic Matter （EOM） of PM0.3-2.5 and PM2.s. These exposures induced several mechanisms of action implied in the genotoxicity, such as oxidative DNA adducts and DNA Damage Response. The toxicity of PM-EOM was higher for the sample including the ultrafine fraction （PM2.5） containing also higher concentrations of polycyclic aromatic hydrocarbons. These results evidenced the major role of organic compounds in the toxicity of PM.展开更多
Human pluripotent stem cells(h PSCs) represent heterogeneous populations, including induced pluripotent stem cells(i PSCs), endogenous plastic somatic cells, and embryonic stem cells(ESCs). Human ESCs are derived from...Human pluripotent stem cells(h PSCs) represent heterogeneous populations, including induced pluripotent stem cells(i PSCs), endogenous plastic somatic cells, and embryonic stem cells(ESCs). Human ESCs are derived from the inner cell mass of the blastocyst, and they are characterized by the abilities to self-renew indefinitely, and to give rise to all cell types of embryonic lineage(pluripotency) under the guidance of the appropriate chemical, mechanical and environmental cues. The combination of these critical features is unique to h ESCs, and set them apart from other human cells. The expectations are high to utilize h ESCs for treating injuries and degenerative diseases; for modeling of complex illnesses and development; for screening and testing of pharmacological products; and for examining toxicity, mutagenicity, teratogenicity, and potential carcinogenic effects of a variety of environmental factors, including ionizing radiation(IR). Exposures to genotoxic stresses, such as background IR, are unavoidable; moreover, IR is widely used in diagnostic and therapeutic procedures in medicine on a routine basis. One of the key outcomes of cell exposures to IR is the change in gene expression, which may underlie the ultimate h ESCs fate after such a stress. However, gaps in our knowledge about basic biology of h ESCs impose a serious limitation to fully realize the potential of h ESCs in practice. The purpose of this review is to examine the available evidence of alterations in gene expression in human pluripotent stem cells after genotoxic stress, and to discuss strategies for future research in this important area.展开更多
Inorganic arsenic induces a variety of toxicities including cancer. The mode of action for cancer and non-cancer effects involves the metabolic generation of trivalent arsenicals and their reaction with sulfhydryl gro...Inorganic arsenic induces a variety of toxicities including cancer. The mode of action for cancer and non-cancer effects involves the metabolic generation of trivalent arsenicals and their reaction with sulfhydryl groups within critical proteins in various cell types which leads to the biological response. In epithelial cells, the response is cell death with consequent regenerative proliferation. If this continues for a long period of time, it can result in an increased risk of cancer. Arsenicals do not react with DNA. There is evidence for indirect genotoxicity in various in vitro and in vivo systems, but these involve exposures at cytotoxic concentrations and are not the basis for cancer development. The resulting markers of genotoxicity could readily be due to the cytotoxicity rather than an effect on the DNA itself. Evidence for genotoxicity in humans has involved detection of chromosomal aberrations, sister chromatid exchanges in lymphocytes and micronucleus formation in lymphocytes, buccal mucosal cells, and exfoliated urothelial cells in the urine. Numerous difficulties have been identified in the interpretation of such results, including inadequate assessment of exposure to arsenic, measurement of micronuclei, and potential confounding factors such as tobacco exposure, folate deficiency, and others. Overall, the data strongly supports a non-linear dose response for the effects of inorganic arsenic. In various in vitro and in vivo models and in human epidemiology studies there appears to be a threshold for biological responses, including cancer.展开更多
文摘BACKGROUND Smoking is a leading cause of carcinogenesis in the head and neck region,representing a critical public health issue.Identifying genotoxic damage in smokers can provide valuable insights for developing preventive interventions.AIM To assess genotoxic damage through the micronucleus assay in exfoliated buccal mucosa cells from users of conventional tobacco,reverse smoking,cannabis,electronic cigarettes,and non-smokers.METHODS A cross-sectional study was conducted with 100 participants divided into five groups:20 conventional tobacco smokers,20 reverse smokers,20 electronic cigarette users,20 cannabis users,and 20 non-smokers.Exfoliated buccal mucosa cells were analyzed using Giemsa and Papanicolaou staining to identify micronuclei(MN)as markers of genotoxic damage.RESULTS MN were present in 86%of the samples.Statistically significant differences were observed in the median micronucleus count between conventional,reverse,and electronic cigarette smokers compared to non-smokers(P<0.001),while no significant difference was found for cannabis smokers(P=0.89).A significant correlation was identified between the presence of oral lesions and micronucleus count(P=0.03).Regression analysis ruled out alcohol as a confounding factor.CONCLUSION This study identified genotoxic damage associated with various smoking habits,except for cannabis use,highlighting the need for public health interventions to reduce smoking and mitigate its genotoxic effects.These findings provide a foundation for future research and the implementation of preventive policies.
文摘Pimpinella anisum,commonly known as anise,is generally used in both folk medicine and the culinary world.In traditional medicine,it is valued for its digestive,respiratory,and antispasmodic properties.This study aims to examine the volatile compounds and antibacterial effect of P.anisum essential oil(PAEO)as well as for the first time its genotoxicity employing both in vitro and computational approaches.Gas chromatography-mass spectrometry(GC-MS)analysis identified anethole as the principal compound,which comprises 92.47%of PAEO.PAEO was tested for its potential antibacterial properties against Bacillus subtilis ATCC 6633,Listeria innocua ATCC 33090,Staphylococcus aureus ATCC 29213,Klebsiella aerogenes ATCC 13048,and a clinical strain of Salmonella enterica serotype Typhi.PAEO displayed noteworthy antibacterial action toward all tested bacteria,especially Staphylococcus aureus,with an inhibition zone of 21.43±0.87 mm,as determined by the disc-diffusion test.Varied between 0.0625%and 2%v/v,while the MBC values ranged from 0.125%to 8%v/v,reflecting the strength of the tested EO.The MBC/MIC ratios indicated the bactericidal nature of PAEO.The results of molecular docking revealed strong binding interactions between key PAEO molecules and microbial target proteins.ADMET(Absorption,Distribution,Metabolism,Excretion,and Toxicity)analysis confirmed favorable pharmacokinetic properties,indicating its potential as a safe therapeutic agent.Additionally,genotoxicity was assessed using the comet assay,which demonstrated minimal genotoxic risk,affirming the oil’s safety.These results highlight the promising antimicrobial properties of PAEO and its possible use as an active agent in the pharmacy,food,and cosmetic sectors.
基金supported by the National Research Centre,Dokki,Cairo,Egypt project#13050302.
文摘Synthesis of zinc oxide nanoparticles(ZnO-NPs)via green method is an outstanding alternative to conventional/regular methods;however,the safety or toxicity of the biosynthesized ZnO-NPs in vivo is not fully explored.This study was conducted to evaluate the protective efficiency of cinnamaldehyde-loaded chitosan nanoparticles(Cin@CSNPs)against oxidative damage and genotoxicity of ZnO-NPs in mice.ZnO-NPs were biosynthesized using the extract of fresh leaves of Mentha pulegium L.Cin was extracted from cinnamon essential oil,and was loaded into chitosan nanoparticle(Cin@CSNPs).Both ZnO-NPs,Cin@CSNPs and CSNPs were characterized.The in vitro release of Cin@CSNPs was determined.In the biological study,6 groups of male BALB/c mice were treated by gavage for 3 weeks as follows,control group,the group received ZnO-NPs(25 mg/kg b.w),the groups received Cin@CSNPs at low dose(50 mg/kg b.w)or high dose(100 mg/kg b.w),and the groups received ZnO-NPs plus Cin@CSNPs at the 2 tested doses.Blood and tissue samples were collected for different biochemical,genetical and histological studies.The particle size of ZnO-NPs,CSNPs,and Cin@CSNPs were(20.78±2.60),(170.0±3.7),and(218.23±2.90)nm,andξ-potential were(32.7±4.6),(8.32±0.27)and(4.80±0.21)mV,respectively.ZnO-NPs disturbed the biochemical and oxidative stress indices,AFP,CEA,TNF-α,chromosomal aberrations in somatic and germ cells,and sperm abnormality along with severe pathological changes in the hepatic,renal,and testicular tissues.Cin@CSNPs improved significantly all the parameters tested and the histological picture in a dose-dependent.Therefore,the biosynthesized ZnO-NPs exhibit oxidative damage and genotoxicity,and Cin@CSNPs have potential protective effects against the risks of ZnO-NPs and may be a promising tool to overcome the challenges of using Cin in food and pharmaceuticals applications.
基金National Nature Science Foundation of China (Grant No.30572350)New Drug Foundation of State Administration of Traditional Chinese Medicine (Grant No.DIX005A)
文摘To further assess hyperoside as a potential new anti-hepatitis B virus （HBV） drug, the safety of hyperoside extracted from Abelmoschus manihot （L.） Medic was evaluated by testing its acute toxicity and mutagenic risk. To test the acute toxicity of hyperoside, we determined the median lethal dose （LD 50 ） in mice. Forty healthy BALB/c mice （20 per sex） were administered a single oral dose of 5000 mg/kg hyperoside via the intragastrical route. The number of animals poisoned and died was noted daily for 14 consecutive days. All animals survived and appeared active and normal, indicating that the LD 50 of hyperoside was more than 5000 mg/kg. Potential genotoxicity of hyperoside was investigated using a bacterial reverse mutation assay （Ames test）, a chromosome aberration test in Chinese hamster lung （CHL） fibroblasts, and an in vivo micronucleus test in rat bone marrow cells. In the bacterial reverse mutation assay, we observed no increases in the number of revertant colonies at any concentrations of hyperoside regardless of metabolic activation （S9） in all tester strains （TA97, TA98, TA100 and TA102） compared to the vehicle control （P0.05）. Hyperoside did not cause significant structural aberration in CHL cells in the presence or absence of S9 （P0.05）. The micronuclei rates of mice bone marrow cell in all groups showed no significant difference when compared with the negative control （P0.05）. In summary, hyperoside showed no genotoxicity in our experimental conditions.
基金supported by Bharathiar University.Tamilnadu,India
文摘Objective:To identify the available phytochemicals and carotenoids in the selected green algae and evaluate the potential genotoxic/antigenotoxic effect using lymphocytes.Methods:Organic,solvent extracts of Chlorococcum humicola(C.humicola)were used for the phytochemical analysis.The available carotenoids were assessed by HPLC,and LC-MS analysis.The genotoxicity was induced by the benzo(a)pyrene in the lymphocyte culture,the genotoxic and antigenotoxic effects of algal carotenoids with and without genotoxic inducer were evaluated by chromosomal aberration(CA),sister chromatid exchange(SCE)and micronucleus assay(MN).Results:The results of the analysis showed that the algae were rich in carotenoids and fatty acids.In the total carotenoids lutein,β-carotene andα-carotene were found to be present in higher concentration.The frequency of CA and SCE increased by benzo(a)pyrene were significantly decreased by the carotenoids(P<0.05 for CA,P<0.001 for SCE).The MN frequencies of the cells were significantly decreased by the treatment with carotenoids when compared with the positive controls(P<0.05).Conclusions:The findings of the present study demonstrate that,the green algae C.humicola is a rich source of bioactive compounds especially carotenoids which effectively fight against environmental genotoxic agents,the carotenoids itself is not a genotoxic substance and should be further considered for its beneficial effects.
基金funded by National High-Tech Research and Development Program(863)of China(No.2013AA062705-1)
文摘Adsorbable organic halogens（AOX） are a general indicator for the total amount of compounds containing organically bonded halogens. AOX concentrations and components were investigated along the wastewater treatment process in four large-scale pharmaceutical factories of China, and genotoxicity based on the SOS/umu test was also evaluated. The results showed that AOX concentrations in wastewater of four factories ranged from 4.6 to 619.4 mg/L, which were high but greatly different owing to differences in the raw materials and products. The wastewater treatment process removed 50.0%–89.9% of AOX, leaving 1.3–302.5 mg/L AOX in the effluents. Genotoxicity levels ranged between 2.1 and 68.0 μg 4-NQO/L in the raw wastewater and decreased to 1.2–41.2 μg 4-NQO/L in the effluents of the wastewater treatment plants（WWTPs）. One of the main products of factory I, ciprofloxacin, was identified as the predominant contributor to its genotoxicity. However, for the other three factories, no significant relationship was observed between genotoxicity and detected AOX compounds.
基金the Tongji University, Shanghai, and the Chongqing University, Chongqing, as part of the MICROTOX project ("Transformation, Bioaccumulation and Toxicity of Organic Micropollutants in the Yangtze Three Gorges Reservoir" No. FKZ 02WT1141)+5 种基金the Sino-German joint environmental research program "Yangtze-Hydro - Sustainable Management of the Newly Created Ecosystem at the Three Gorges Dam" (No. FKZ 02WT Bergmann et al. (2011) www.yangtzeproject.de)part of the research cluster "Pollutants/Water/Sediment-Impacts of Transformation and Transportation Processes on the Yangtze Water Quality"supported by a cooperation project with Chinese colleagues also sponsored by the Federal Ministry of Education and Research, Germany (No. DLR FKZ 01DO12007)the Chinese 111 Program
文摘Besides obvious benefits,the Three Gorges Dam＇s construction resulted in new pollution scenarios with the potentials to threaten the Three Gorges Reservoir（TGR） ecosystem.In order to record organic contamination,to find links to ecotoxicological impacts and to serve as reference for ensuing monitoring,several sites in the TGR area were screened applying the triad approach with additional lines-of-evidence as a holistic assessment method.Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011 and 2012 to determine organic pollution levels,mutagenic potentials and genotoxic impacts.Two regional hot-spots near the cities of Chongqing and Kaixian were identified and further investigated in 2013.Only polycyclic aromatic hydrocarbons（PAHs） could be detected in sediments in 2011（165-1653 ng/g）,emphasizing their roles as key pollutants of the area.Their ubiquity was confirmed at Chongqing（150-433 ng/g） and Kaixian（127-590 ng/g） in2013.Concentrations were comparable to other major Chinese and German rivers.However,the immense sediment influx suggested a deposition of 216-636 kg PAH/day（0.2-0.6 mg PAH/（m2·day））,indicating an ecotoxicological risk.PAH source analysis highlighted primary impacts of combustion sources on the more industrialized upper TGR section,whereas petrogenic sources dominated the mid-low section.Furthermore,sediment extracts from several sites exhibited significant activities of frameshift promutagens in the Ames fluctuation assay.Additionally,significant genotoxic impairments in erythrocytes of P.vachellii were detected（Chongqing/Kaixian）,demonstrating the relevance of genotoxicity as animportant mode of action in the TGR＇s fish.PAHs,their derivatives and non-target compounds are considered as main causative agents.
基金supported by the National Natural Science Foundation of China (No. 50838005)the Program for Changjiang Scholars and Innovative Research Team inUniversity (No. IRT0853)the National Program of Water Pollution Control (No. 2008ZX07317-004)
文摘The freshwater luminescent bacteria Vibrio-qinghaiensis sp.-Q67 test and the Vicia faba root tip test associated with solid-phase extraction were applied for cytotoxicity and genotoxicity assessment of organic substances in three rivers, two lakes and effluent flows from two wastewater treatment plants （WWTPs） in Xi＇an, China. Although the most seriously polluted fiver with high chemical oxygen demand （COD） and total organic carbon （TOC） showed high cytotoxicity （expressed as TIIs0, the toxicity impact index） and genotoxicity （expressed as RMCN, the relative frequency of micronucleus）, no correlative relation was found between the ecotoxicity and organic content of the water samples. However, there was a linear correlative relation between TIIs0 and RMCN for most water samples except that from the Zaohe River, which receives discharge from WWTP and untreated industrial wastewaters. The ecotoxicity of the organic toxicants in the Chanhe River and Zaohe River indicated that cytotoxic and genotoxic effects were related to the pollutant source. The TII50 and RMCN were also found to correlate roughly to the dissolved oxygen concentration of the water. Sufficient dissolved oxygen in surface water is thus proved to be an indicator of a healthy water environmental condition.
基金The Society Development Foundation of Jiangsu Province (No. BS2001039)
文摘An increasing number of industrial, agricultural, and commercial chemicals in the aquatic environment leads to various deleterious effects on organisms, which is becoming an increasingly serious problem in China. In this study, the comet assay was conducted to investigate the genotoxicity to human body caused by organic concentrates in the drinking water sources of Nanjing City from Yangtze River of China, and health and ecology risk due to expose to these organic pollutants were evaluated with the multimedia environmental assessment system （MEAS）. For all the water samples, they were collected from four different locations in the drinking water sourcr samples, es of Nanjing City. The results of the comet assay showed that all the organic concentrates from the water samples could induce different levels DNA damages on human peripheral blood lymphocytes, and a statistically significant difference （p〈0.01） was observed compared with the solvent control, which demonstrated the genotoxicity was in existence. According to the ambient severity （AS） of individual compound, we had sorted out the main organic pollutants in the drinking water source of the four waterworks, and the results showed that there was some potential hazard to human body for all the source water, namely the total ambient severity （TAS） of health for each water source was more than 1. However, the TAS of ecology for each water source was less than 1, which indicated that it was safe to ecology. The results of this investigation demonstrate the application of the comet assay and the MEAS in aquatic environmental monitoring studies, and the comet assay found to be fast, sensitive, and suitable for genotoxicity monitoring programs of drinking water source.
文摘The disinfection of drinking water is an important public health service that generates high quality, safe and palatable tap water. The disinfection of drinking water to reduce waterborne disease was an outstanding public health achievement of the 20 th century.An unintended consequence is the reaction of disinfectants with natural organic matter,anthropogenic contaminants and bromide/iodide to form disinfection by-products（DBPs）.A large number of DBPs are cytotoxic, neurotoxic, mutagenic, genotoxic, carcinogenic and teratogenic. Epidemiological studies demonstrated low but significant associations between disinfected drinking water and adverse health effects. The distribution of DBPs in disinfected waters has been well defined by advances in high precision analytical chemistry. Progress in the analytical biology and toxicology of DBPs has been forthcoming.The objective of this review was to provide a detailed presentation of the methodology for the quantitative, comparative analyses on the induction of cytotoxicity and genotoxicity of103 DBPs using an identical analytical biological platform and endpoints. A single Chinese hamster ovary cell line was employed in the assays. The data presented are derived from papers published in the literature as well as additional new data and represent the largest direct quantitative comparison on the toxic potency of both regulated and emerging DBPs.These data may form the foundation of novel research to define the major forcing agents of DBP-mediated toxicity in disinfected water and may play an important role in achieving the goal of making safe drinking water better.
基金supported by the National Natu-ral Sciences Foundation of China (No. 50525824)the Tianjin Special Innovation Fund (No. 06FZZDSH00900,TJZX1-YW03)the National Water Project (No.2008ZX07314-003)
文摘The effects of ozonation on the formation potential of typical disinfection byproducts （DBPs） and the changes of genotoxicity during post chlorination of tertiary effluent from a sewage treatment plant were investigated. Ozonation enhanced the yields of all detected chlorine DBPs except CHCI3. At a chlorine dose of 5 mg/L, the three brominated THMs and five HAAs increased, while chloroform decreased with the increase of ozone dose from 0 to 10 mg/L （ozone dose in consumption base）. At a chlorine dose of 10 mg/L, the two mixed bromochloro species THMs and two dominant HAAs （DCAA and TCAA） increased firstly and then decreased with the increase of ozone dose, with the turning point approximately occurring at an ozone dose of 5 mg/L. The genotoxicity detected using umu test, on the other hand, was removed from 7 Ixg 4-NQO/L to a negligible level by ozonation under an ozone dose of 5 mg/L. Chlorination could further remove the genotoxicity to some extent. It was found that SUVA （UV absorbance divided by DOC concentration） might be used as an indicative parameter for monitoring the removal of genotoxicity during the oxidation.
文摘Objective: To assess and compare the cytotoxic, genotoxic, apoptotic and reactive oxygen species(ROS) generating effects of naringenin(NG) and its new derived compound naringenin-oxime(NG-Ox) on MCF-7, HT-29, PC-12 cancer and L-929 normal cell lines.Methods: The cells were incubated with different doses of NG-Ox and NG(50–1 000 mmol/L) for 24 h. The cell viability was assessed based on ATP cell viability assay.Intracellular accumulation of ROS was determined using the fluorescent probes 2070-dichlorodihydrofluorescin diacetate. Genotoxic effects were evaluated by alkaline single cell gel electrophoresis assay(comet assay) and, the apoptotic effect was evaluated by acridine orange staining at below the IC50 levels.Results: Both NG-Ox and NG exhibited cytotoxic, genotoxic and apoptotic effects and resulted in increased ROS values in a dose-dependent manner. The effects were more pronounced on cancer cell lines. The cytotoxic, genotoxic and apoptotic effects of NG-Ox were higher than that of NG in all cell lines. Significant correlations were observed between cell viability, DNA damage, apoptosis and ROS, in all cell lines exposed to either NG-Ox or NG.Conclusions: This study showed that both NG-Ox and NG possess cytotoxic, genotoxic and apoptotic activities through the production of ROS on cells, NG-Ox being the more effective one. Therefore, derived compound of NG might be used as antiproliferative agents for the treatment of cancer.
文摘The following experiments were conducted to evaluate the genotoxic effects of GMA (glycidyl methacrylale) on mammalian and human cells.(1) Using the absorption spectrum shift method in vitro, we observed that the maximums of calf thymus DNA and GMA were shifted toward longer wavelengths (a change of more than 15nm) and the absorbance decreased after incubation at room temperature for 15min or more.The result indicates that binding of DNA and GMA had occurred.The binding force is strong, not affected by the addition of concentrated sodium chloride solution, and only slightly decreased by the addition of 8 M urea solution.Therefore the bond between DNA and GMA might be covalent.(2) In cell cultures, unscheduled DNA synthesis (UDS) in human and/or rat lymphocyte was induced and DNA semiconserva-tive replication was inhibited by GMA at concentrations of less than 5.2 mM.(3) Sperm abnormality tests and assays of UDS in germ cells of male mice were conducted to study the in vivo genotoxicity of GMA.The results revealed that GMA could damage DNA, increase sperm abnormality frequency, and reduce the number of sperm cells, 1990 Academic Press.Inc.
基金supported by Ankara University, Management of Scientific Research Projects with No. 2003- 0705080
文摘Lichens are widely used in biomonitoring studies of air pollution, either as bioindicators of air quality or as bioaccumulators of atmospheric deposition. Over the past decade, several molecular techniques have been developed to provide information on diversity, genotoxicology, genetic relationships, etc. The heavy metal contents of Evernia prunastri samples were determined by atomic absorption spectrometry. The Random Amplified Polymorphic DNA Polymerase Chain Reaction （RAPD-PCR） method was used to describe the pattern of DNA band variation in the samples influenced by the environmental pollution. The study was designed to describe the level of pollution in an area contaminated with smoke and waste from an iron-steel factory, and to reveal the level of potential genotoxic agents around this source of pollution. The study also examined the suitability of the lichen samples for the detection of genotoxicity.
基金supported by USM Short Term Grant(304/CIPPM/6312034)from Universiti Sains Malaysia
文摘Objective:To evaluate the cytotoxicity and genotoxicity activity of Euphorbia hirta(E.hirta)in MCF-7 cell line model using comet assay.Methods:The cytotoxicity of E.hirta extract was investigated by employing brine shrimp lethality assay and the genotoxicity of E.hirta was assessed by using Comet assay.Results:Both toxicity tests exhibited significant toxicity result.In the comet assay,the E.hirta extract exhibited genotoxicity effects against MCF-7 DNA in a time-dependent manner by increasing mean percentage of DNA damage.The extract of E.hirta showed significant toxicity against brine shrimp with an LC_(50)value of 620.382μg/mL(24 h).Comparison with positive control potassium dichroniate signifies that cytotoxicity exhibited by the methanol extract might have moderate activity.Conclusion:The present work confirmed the cytotoxicity and genotoxicity of E.hirta.However,the observed toxicity of E.hta extracts needs to be confirmed in additional studies.
文摘Objective Many studies have been conducted in order to evaluate the genotoxicity of chemicals and waste materials, which utilized in vivo test protocols. The use of animals for routine toxicity testing is now questioned by a growing segment of society. Methods Keeping the above fact in mind, we have conducted in the present study the genotoxicity evaluation of oily sludge samples generated from a petroleum refinery and petrochemical industry and ETP sludge from petroleum refinery using DNA damage, chromosomal aberration, p53 protein induction and apoptosis in short term in vitro mammalian Chinese Hamster Ovary cell cultures. Results It is evident from the results that the oily sludge compounds derived from petroleum refinery and petrochemical industry could cause DNA damage, chromosomal aberration, p53 protein accumulation and apoptotic cell death on exposure to oily sludge extracts in the presence of metabolic activation system (S-9 mix), however, ETP sludge extract could not cause significant genotoxicity in comparison to oily sludge extract and negative control. Conclusion The effect may be attributed to polycyclic aromatic hydrocarbons present in the samples as evidenced from GC-MS.
基金supported by the Key Research and Development Program of Shandong Province(Grant No.:2019GSF111001)the National Natural Science Foundation of China(Grant No.:21906096)+2 种基金the Youth Science Funds of the Shandong Academy of Sciences(Grant No.:2019QN009)the Youth Ph.D.Cooperation Funds of Qilu University of Technology(Shandong Academy of Sciences,Grant No.:2018BSHZ0029)the Program for Taishan Scholars of Shandong Province(Grant No.:tsqn202103099).
文摘Covalent organic nanospheres(CONs)were explored as a fiber coating for solid-phase microextraction of genotoxic impurities(GTIs)from active ingredients(AIs).CONs were synthesized by an easy solutionphase procedure at 25℃.The obtained nanospheres exhibited a high specific surface area,good thermostability,high acid and alkali resistance,and favorable crystallinity and porosity.Two types of GTIs,alkyl halides(1-iodooctane,1-chlorobenzene,1-bromododecane,1,2-dichlorobenzene,1-bromooctane,1-chlorohexane,and 1,8-dibromooctane)and sulfonate esters(methyl p-toluenesulfonate and ethyl ptoluenesulfonate),were chosen as target molecules for assessing the performance of the coating.The prepared coating achieved high enhancement factors(5097-9799)for the selected GTIs.The strong affinity between CONs and GTIs was tentatively attributed to π-π and hydrophobicity interactions,large surface area of the CONs,and size-matching of the materials.Combined with gas chromatography-mass spectrometry(GC-MS),the established analytical method detected the GTIs in capecitabine and imatinib mesylate samples over a wide linear range(0.2-200 ng/g)with a low detection limit(0.04-2.0 ng/g),satisfactory recovery(80.03%-109.5%),and high repeatability(6.20%-14.8%)and reproducibility(6.20%-14.1%).Therefore,the CON-coated fibers are promising alternatives for the sensitive detection of GTIs in AI samples.
基金supported by the Institut National du Cancer (INCa Convention no. 2010-368)+2 种基金the Hauts-de-France Region (Convention No. 14003399)the French Agency of the Environment and Energy (ADEME Convention no. 1494c008283-84)
文摘Particulate matter in ambient air constitutes a complex mixture of fine and ultrafine particles composed of various chemical compounds including metals, ions, and organics. A multidisciplinary approach was developed by studying physico-chemical characteristics and mechanisms involved in the toxicity of particulate atmospheric pollution. PM0.3-2.s and PM2.5 including ultrafine particles were sampled in Dunkerque, a French industrialized seaside city. PM samples were characterized from a chemical and toxicological point of view. Physico-chemical characterization evidenced that PM2.5 comes from several sources： natural ones, such as soil resuspension and marine sea-salt emissions, as well as anthropogenic ones, such as shipping traffic, road traffic, and industrial activities. Human BEAS-2B tung cells were exposed to PM0.3-2.5, or to the Extractable Organic Matter （EOM） of PM0.3-2.5 and PM2.s. These exposures induced several mechanisms of action implied in the genotoxicity, such as oxidative DNA adducts and DNA Damage Response. The toxicity of PM-EOM was higher for the sample including the ultrafine fraction （PM2.5） containing also higher concentrations of polycyclic aromatic hydrocarbons. These results evidenced the major role of organic compounds in the toxicity of PM.
基金Supported by The Intramural Research Program of the National Institutes of Health,Clinical Center
文摘Human pluripotent stem cells(h PSCs) represent heterogeneous populations, including induced pluripotent stem cells(i PSCs), endogenous plastic somatic cells, and embryonic stem cells(ESCs). Human ESCs are derived from the inner cell mass of the blastocyst, and they are characterized by the abilities to self-renew indefinitely, and to give rise to all cell types of embryonic lineage(pluripotency) under the guidance of the appropriate chemical, mechanical and environmental cues. The combination of these critical features is unique to h ESCs, and set them apart from other human cells. The expectations are high to utilize h ESCs for treating injuries and degenerative diseases; for modeling of complex illnesses and development; for screening and testing of pharmacological products; and for examining toxicity, mutagenicity, teratogenicity, and potential carcinogenic effects of a variety of environmental factors, including ionizing radiation(IR). Exposures to genotoxic stresses, such as background IR, are unavoidable; moreover, IR is widely used in diagnostic and therapeutic procedures in medicine on a routine basis. One of the key outcomes of cell exposures to IR is the change in gene expression, which may underlie the ultimate h ESCs fate after such a stress. However, gaps in our knowledge about basic biology of h ESCs impose a serious limitation to fully realize the potential of h ESCs in practice. The purpose of this review is to examine the available evidence of alterations in gene expression in human pluripotent stem cells after genotoxic stress, and to discuss strategies for future research in this important area.
文摘Inorganic arsenic induces a variety of toxicities including cancer. The mode of action for cancer and non-cancer effects involves the metabolic generation of trivalent arsenicals and their reaction with sulfhydryl groups within critical proteins in various cell types which leads to the biological response. In epithelial cells, the response is cell death with consequent regenerative proliferation. If this continues for a long period of time, it can result in an increased risk of cancer. Arsenicals do not react with DNA. There is evidence for indirect genotoxicity in various in vitro and in vivo systems, but these involve exposures at cytotoxic concentrations and are not the basis for cancer development. The resulting markers of genotoxicity could readily be due to the cytotoxicity rather than an effect on the DNA itself. Evidence for genotoxicity in humans has involved detection of chromosomal aberrations, sister chromatid exchanges in lymphocytes and micronucleus formation in lymphocytes, buccal mucosal cells, and exfoliated urothelial cells in the urine. Numerous difficulties have been identified in the interpretation of such results, including inadequate assessment of exposure to arsenic, measurement of micronuclei, and potential confounding factors such as tobacco exposure, folate deficiency, and others. Overall, the data strongly supports a non-linear dose response for the effects of inorganic arsenic. In various in vitro and in vivo models and in human epidemiology studies there appears to be a threshold for biological responses, including cancer.
