Gulati D K, Witt K, Anderson B, Zeiger E, Shelby M D
Environmental Health Research and Testing, Inc., Lexington, Kentucky.
Environ Mol Mutagen. 1989;13(2):133-93. doi: 10.1002/em.2850130208.
Twenty-seven chemicals previously tested in rodent carcinogenicity assays were tested for induction of chromosomal aberrations (ABS) and sister chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells as part of a larger analysis of the correlation between results of in vitro genetic toxicity assays and carcinogenicity bioassays. Chemicals were tested up to toxic doses with and without exogenous metabolic activation. Seventeen of the chemicals tested were carcinogens; only two of these were negative for both ABS and SCE. Of the eight noncarcinogens tested, four were negative for both endpoints (ABS and SCE) and four gave a positive response for at least one endpoint. Of the remaining two chemicals, one, diallyl phthalate, gave an equivocal response in the bioassay and a positive response in these CHO cell cytogenetics tests. The other chemical, 2,4-toluene diisocyanate, was tested for carcinogenicity as a mixture with the 2,6-isomer; the mixture was carcinogenic, but the cytogenetic test results for the 2,4-isomer were negative. Only six of the 27 chemicals tested produced an effect in one endpoint alone; the other 21 were either positive or negative for both ABS and SCE. Only one of the 27 chemicals tested required S9 for a positive response in the SCE test; two chemicals required S9 for a positive result in the ABS test. Experiments with unsynchronized CHO cells demonstrated that mean SCE frequency increased with increasing culture time, and this may have been a factor in the positive results obtained for five chemicals in the SCE test under conditions of delayed harvest.
作为体外遗传毒性试验结果与致癌性生物测定之间相关性的一项更大规模分析的一部分，对之前在啮齿动物致癌性试验中测试过的27种化学物质进行了检测，以观察其对中国仓鼠卵巢（CHO）细胞染色体畸变（ABS）和姐妹染色单体交换（SCE）的诱导作用。在有和没有外源性代谢激活的情况下，对化学物质进行了高达毒性剂量的测试。所测试的17种化学物质是致癌物；其中只有两种在ABS和SCE检测中呈阴性。在所测试的8种非致癌物中，4种在两个终点（ABS和SCE）检测中均呈阴性，4种在至少一个终点检测中呈阳性反应。在其余两种化学物质中，一种邻苯二甲酸二烯丙酯在生物测定中给出了模棱两可的反应，而在这些CHO细胞细胞遗传学测试中呈阳性反应。另一种化学物质2,4-甲苯二异氰酸酯与2,6-异构体的混合物进行了致癌性测试；该混合物具有致癌性，但2,4-异构体的细胞遗传学测试结果为阴性。所测试的27种化学物质中只有6种仅在一个终点产生了效应；其他21种在ABS和SCE检测中均为阳性或阴性。所测试的27种化学物质中只有1种在SCE测试中呈阳性反应需要S9；2种化学物质在ABS测试中呈阳性结果需要S9。对未同步化的CHO细胞进行的实验表明，平均SCE频率随着培养时间的增加而增加，这可能是在延迟收获条件下5种化学物质在SCE测试中获得阳性结果的一个因素。
