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苯酰甲硝唑致突变致畸性研究

MUTAGENICITY STUDY OF THE BENZOYLMETRONIDAZOLE
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摘要 本研究采用Ames试验、细胞染色体畸变和小鼠胚胎致畸试验,旨在探索新研制的苯酞甲硝唑是否具致突变性。Ames试验结果表明,药物剂量的回复突变菌落数明显高于自发回变数,与阳性对照组相近。体外培养CHO-k细胞株染色体畸变试验结果表明,药物剂量组在加活化代谢和非活化代谢条件下,细胞染色体畸变率没有增加,对细胞DNA损伤不明显。在哺乳动物胚胎致畸试验中,药物高剂量组(5.0g/kg)对胚胎产生了毒性效应,吸收胎和死胎率升高,活胎率降低,检查活鼠的生长发育和骨骼未发现明显的畸形。其余药物组对小鼠胚胎性不明显。 Benzoylmetronidazole, the first effective drug against trichomas vaginalis, has recently been used in the treatment of anaerobic bacterial infections, Crohn' disease and as radiosensitizer in conjunction with radiotherapy. The research result of benzoylmetronidazole mutagenesis effects were evaluated. The results showed that all these drugs at various concentrations (5.0mg/plate, 2.5mg/plate 1.25mg/plate 0.62mg/plate)produced mutagenic effect on 4 strains (TA98 TA97 TA100 and TA102) in Ames test. Induction by benzoylmetronidazole of chromosome aberrations in Chinese Hamster Ovary cells (CHO) were evaluated. The cells were grown in Eagles minimum essential medium supplemented with 10% fetal calfserum (PH7.2) .Chromsome aberrations were examined on 100 metaphase plates for each dose. The results showed that 5 drugs concentrations (5.0mg/ml, 2.5mg/ ml 1.25mg/m 10.62mg/mland 0.312mg/ml) not produced cell chromosome aberrations. The result of benzoylmetronidazole teratogenicity and embyrotoxicity effects were evaluated in mice. Benzoylmetronidazole were administered orally at 0.5,1.0, 2.0,4.0g/kg respectively mixed with rape oil 6-15 day after gestation.The results showed that denzoylmetronidazole within these doses did not induce teratogenicityand embryotoxicity, as measured by percentage of pead and absorbed fetuses, mean fetal weight, length of; body and of tail compared to negative control group (5mg/kg) showed major increased of teratogenicity and embyrotoxicity effects. The results concluded a statistically significant difference between benzoylmetronidazole and cyclophosphamids group(P<0.01).
出处 《癌变·畸变·突变》 CAS CSCD 1992年第3期5-8,共4页 Carcinogenesis,Teratogenesis & Mutagenesis
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