甲硝唑及其两种尿液代谢物在体外对人淋巴细胞无遗传毒性作用。

Absence of genotoxic effects of metronidazole and two of its urinary metabolites on human lymphocytes in vitro.

作者信息

Lambert B, Lindblad A, Ringborg U

出版信息

Mutat Res. 1979 Jul;67(3):281-7. doi: 10.1016/0165-1218(79)90022-3.

Abstract

The antiprotozoan agent metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) and two of its major human urinary excretion products, 2-methyl-5-nitromidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole were tested for genotoxic activity in human lymphocytes in vitro by analysis of chromosome aberrations, sister-chromatid exchanges and DNA-repair synthesis. The positive control compounds methyl methanesulphonate (MMS) and nitrogen mustard (HN2) showed significant genotoxic activity in these tests. No such activity of metronidazole and its two metabolites was detected in concentrations up to 1000 microgram/ml (5.8 X 10(-3) M). Nor did these 3 compounds influence DNA-repair synthesis induced by MMS and HN2. These results suggest that metronidazole, 2-methyl-5-nitroimidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole have no direct genotoxic effect on human lymphocytes in vitro.

摘要

通过分析染色体畸变、姐妹染色单体交换和DNA修复合成，对抗原生动物药物甲硝唑（1-(2-羟乙基)-2-甲基-5-硝基咪唑）及其两种主要的人体尿液排泄产物2-甲基-5-硝基咪唑-1-基乙酸和1-(2-羟乙基)-2-羟甲基-5-硝基咪唑进行了体外人淋巴细胞遗传毒性活性测试。阳性对照化合物甲磺酸甲酯（MMS）和氮芥（HN2）在这些测试中显示出显著的遗传毒性活性。在浓度高达1000微克/毫升（5.8×10⁻³M）时，未检测到甲硝唑及其两种代谢产物的此类活性。这3种化合物也未影响由MMS和HN2诱导的DNA修复合成。这些结果表明，甲硝唑、2-甲基-5-硝基咪唑-1-基乙酸和1-(2-羟乙基)-2-羟甲基-5-硝基咪唑在体外对人淋巴细胞没有直接的遗传毒性作用。