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通过体外遗传毒性试验预测啮齿动物的化学致癌性。

Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays.

作者信息

Tennant R W, Margolin B H, Shelby M D, Zeiger E, Haseman J K, Spalding J, Caspary W, Resnick M, Stasiewicz S, Anderson B

出版信息

Science. 1987 May 22;236(4804):933-41. doi: 10.1126/science.3554512.

DOI:10.1126/science.3554512
PMID:3554512
Abstract

Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays.

摘要

对四种广泛使用的遗传毒性体外检测方法预测特定化学物质在啮齿动物中致癌性的能力进行了评估。这些检测方法包括沙门氏菌和小鼠淋巴瘤细胞中的诱变试验,以及中国仓鼠卵巢细胞中的染色体畸变和姐妹染色单体交换试验。本评估使用了最近在美国国立癌症研究所和国家毒理学计划进行的两年致癌性研究中测试的73种化学物质。四种体外检测方法的测试结果与啮齿动物致癌性结果的个体一致性没有显著差异;每种检测方法的一致性约为60%。在本研究的范围内,没有证据表明这四种检测方法之间具有互补性,并且由这些检测方法构建的任何一组检测在沙门氏菌检测的整体性能上都没有显著改善。代表三种细胞类型和四个终点的体外检测方法之间确实显示出实质性的一致性,这表明在一种体外检测中呈阳性的化学物质在其他体外检测中也往往呈阳性。

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