Genetic toxicity of taxol

研究了抗肿瘤新药紫杉醇的致突变性及致癌潜能，结果表明，紫杉醇在１～５０００μｇ／皿范围内，无论有无Ｓ９活化系统对沙门氏菌株四株（ＴＡ９７，ＴＡ９８，ＴＡ１００，ＴＡ１０２）标准测试菌株均无致突变性．但在小鼠骨髓细胞微核试验和ＣＨＬ细胞染色体畸变分析试验中，均显示了阳性反应．紫杉醇在２０，４０，８０ｍｇ·ｋｇ－１诱导的小鼠骨髓多染红细胞微核率分别为１９．３‰，２９．３‰，４７．１‰，均明显高于阴性对照的２．２‰（Ｐ＜０．０１）。染色体畸变分析表明，非活化条件下在２０～１６０μｇ·Ｌ－１范围内，活化条件下在８０～６４０μｇ·Ｌ－１范围内，紫杉醇可使ＣＨＬ细胞染色体畸变增加．畸变类型主要为染色体数目改变，表明其作用点是纺缍体而不是ＤＮＡ．本研究结果显示了紫杉醇的致癌潜能，也为其临床应用的风险效益评价提供了有价值的资料．关键词紫杉醇；沙门氏菌；微核；染色体畸变

Genetic toxicity of taxol

The present study was aimed to investigate the mutagenicity and carcinogenic potential of taxol, a novel antitumour agent. The results showed that taxol, at the concentrations of 1.0 μg-5.0 mg/plate, both with and without S9 activation, was not mutagenic to the four standard test strains (TA97, TA98, TA100 and TA102) in the Salmonella mutagenicity test, and showed positive responses in both mouse bone marrow micronucleus assay and chromosomal aberration analysis of CHL cells. The micronucleus rate induced by taxol at concentrations of 20, 40 and 80 mg·kg^-1 was 19.3, 29.3 and 47.1‰ respectively, which differed considerably from the control (2.2‰). The activities of taxol on chromosomal aberration of CHL cell were also demonstrated in the range of 20-160 μg·L^-1 without S9 activation and 80-640 μg·L^-1 with S9 activation. These aberrations were characterized by the numeral aberrations of chromosome, contrary to those induced by positive control mutagens. These results are consistent with the ability of taxol to inhibit tubulin disassembly in dividing cells, and indicate that its action target is the spindle rather than the DNA. The present study shows a carcinogenic potential of taxol and provides valuable data for the risk-benefit analysis of its clinical use.