摘要
目的评价9-[2-（膦酰甲氧基）乙基]腺苷-钠盐（PMEA-Na）的致突变性.方法采用组氨酸缺陷型鼠伤寒沙门氏菌回复突变试验（Ames试验）、中国仓鼠肺细胞（CHL）染色体畸变试验和小鼠骨髓微核试验,观察PMEA-Na的致突变性.结果 PMEA-Na在50～5000 μg·皿^-1剂量范围内,加与不加S9活化系统条件下,对TA97、TA98、TA100、TA102四种菌株的回变菌落数均未超过自发对照的2倍,即Ames试验结果为阴性;染色体畸变试验中,当药物浓度为48、24、12、6 mg·L^-1时,活化条件下各浓度细胞的染色体畸变率均低于5%.在非活化条件下,药物浓度为48 mg·L^-1培养48 h时,染色体畸变率为10%,因此染色体畸变试验结果为阳性;小鼠静脉注射PMEA-Na剂量为1 000、500、250 mg·kg^-1时,骨髓中含微核的嗜多染红细胞数明显增加,即微核试验结果为阳性.结论在本实验条件下,PMEA-Na具有潜在的致突变性.
Aim To evaluate the mutagenicity of sodium 9-[ 2-（phosphonomethoxy） ethyl ] adenine （PEMA-Na）. Methods The mutagenicity testing of PEMA-Na was performed, including gene reverse mutation test of Salmonella typhimarium histamine-auxotroph, chromosomal aberrations test of China Hamster lung cells （CHL） and analysis of micronuclei in bone marrow cells of mice. Results In the concentration range of 50 - 5000 μg per plate, the reverse mutation numbers of four strains TA97 ,TAgs ,TA100 ,TA102 didn＇ t surpass twice those in spontaneous control, namely negative; In vitro chromosomal aberrations test of CHL, when the treated dosage was 48,24,12,6 mg· L^-1 ,the ratios of aberration were below 5% with metabolic activation system. But when CHL were exposed to PEMA-Na （48 mg · L^-1） for 48h without metabolic activation system, the ratio of aberration was 10% ,namely positive. When PEMA-Na was formulated for intravenous injection to mice in dosages 1000,500, 250 mg kg^-1, the numbers of micronucleus in polychromatocytes increased obviously,namely positive. Conclusion The results show that PEMA-Na has potential mutagenicity.
出处
《安徽医药》
CAS
2006年第6期410-412,共3页
Anhui Medical and Pharmaceutical Journal
