Schiestl R H, Gietz R D, Mehta R D, Hastings P J
Department of Biology, University of Rochester, NY 14627.
Carcinogenesis. 1989 Aug;10(8):1445-55. doi: 10.1093/carcin/10.8.1445.
To identify environmental carcinogens there is a need for inexpensive and reliable short-term tests that can be used to predict the carcinogenic potential of any given substance with high accuracy. The Ames assay, which is based on the induction of mutations in Salmonella typhimurium, is the most extensively used short-term test but certain human or animal carcinogens exist that are persistently undetectable as mutagens with the Ames assay or with other short-term tests. There is a need for a short-term test to detect those carcinogens that are missed by the Ames assay. Carcinogenesis is in many cases associated with genome rearrangement. Because of this association a system screening for intrachromosomal recombination that results in genome rearrangement has been constructed for potential use as a short-term test in the yeast Saccharomyces cerevisiae. Evaluation of this recombination system shows that it is readily inducible by a variety of mutagenic as well as non-readily inducible by a variety of mutagenic as well as non-mutagenic carcinogens, including carcinogens that are not detectable by the Ames assay or by various other short-term tests, such as safrole, urethane, ethionine, auramine, methylene chloride, carbon tetrachloride, cadmium sulfate, aniline, dimethylhydrazine, aminotriazole, acetamide, thiourea and DDE. The present report shows the data for these as well as for additional agents, their response profiles with different concentrations of the agents and the protocol for the DEL system.
为了识别环境致癌物,需要廉价且可靠的短期测试,这些测试可用于高精度预测任何给定物质的致癌潜力。基于鼠伤寒沙门氏菌中突变诱导的艾姆斯试验是使用最广泛的短期测试,但存在某些人类或动物致癌物,用艾姆斯试验或其他短期测试持续检测不到其致突变性。需要一种短期测试来检测那些被艾姆斯试验遗漏的致癌物。在许多情况下,致癌作用与基因组重排有关。由于这种关联,构建了一种用于筛选导致基因组重排的染色体内重组的系统,有可能用作酿酒酵母中的短期测试。对该重组系统的评估表明,它很容易被多种诱变剂诱导,也容易被多种诱变剂以及非诱变剂致癌物诱导,包括那些用艾姆斯试验或其他各种短期测试检测不到的致癌物,如黄樟素、氨基甲酸乙酯、乙硫氨酸、金胺、二氯甲烷、四氯化碳、硫酸镉、苯胺、二甲基肼、氨基三唑、乙酰胺、硫脲和滴滴涕。本报告展示了这些以及其他试剂的数据、它们在不同浓度试剂下的反应谱以及DEL系统的方案。