Mayer V W
Genetics. 1973 Jul;74(3):433-42. doi: 10.1093/genetics/74.3.433.
Dimethylnitrosamine and diethylnitrosamine, two potent carcinogens, are nonmutagenic when tested directly in microorganisms. Likewise 1-naphthylamine and 2-naphthylamine are also nonmutagenic but the N-hydroxy derivatives are mutagenic in microorganisms. Apparently these compounds require metabolism to breakdown products which are then the proximately active agents, and microorganisms lack the enzymes necessary to effect this conversion. These compounds are mutagenic in Saccharomyces after conversion to breakdown products in an in vitro hydroxylation medium. The induction of mitotic crossing over in Saccharomyces cerevisiae by breakdown products of dimethylnitrosamine, diethylnitrosamine, 1-naphthylamine and 2-naphthylamine formed in the Udenfriend hydroxylation medium is reported in this communication. Mitotic crossing over was detected as red sectored colonies resulting from induced homozygosity of the ade2 marker. Dimethylamine and diethylamine, which lack the nitroso group of the nitrosamines, did not induce mitotic crossing over under any of the test conditions. To further confirm that the induced sectored colonies were the result of mitotic crossing over they were tested for the presence of reciprocal products. The expected reciprocal products were found in over 67% of the isolates tested. The significance and practicality of using mitotic recombination as an indicator of genetic damage potential of chemicals is discussed.
二甲基亚硝胺和二乙基亚硝胺这两种强效致癌物,在直接对微生物进行测试时无致突变性。同样,1-萘胺和2-萘胺也无致突变性,但它们的N-羟基衍生物在微生物中具有致突变性。显然,这些化合物需要代谢为分解产物,这些分解产物才是直接的活性剂,而微生物缺乏实现这种转化所需的酶。在体外羟基化培养基中转化为分解产物后,这些化合物在酿酒酵母中具有致突变性。本文报道了在乌登弗里德羟基化培养基中形成的二甲基亚硝胺、二乙基亚硝胺、1-萘胺和2-萘胺的分解产物对酿酒酵母有丝分裂交换的诱导作用。有丝分裂交换通过ade2标记的纯合性诱导产生的红色扇形菌落来检测。缺乏亚硝胺亚硝基的二甲胺和二乙胺在任何测试条件下均未诱导有丝分裂交换。为进一步证实诱导的扇形菌落是有丝分裂交换的结果,对其进行了互作产物检测。在所检测的分离物中,超过67%发现了预期的互作产物。本文还讨论了使用有丝分裂重组作为化学物质遗传损伤潜力指标的意义和实用性。