Ivanovic V, Weinstein I B
Cancer Res. 1980 Oct;40(10):3508-11.
In the present study, the induction of base-pair reversion mutations from trp to Trp+ in the wild type and in uvrA, recA, and lexA mutants of Escherichia coli B/r was used to analyze the mechanism of benzo(a)pyrene-7,8-dihydrodiol 9,10-oxide (BPDE) mutagenesis. BPDE mutagenesis was compared to that of two well characterized mutagens: ethyl methanesulfonate and 4-nitroquinoline 1-oxide. We found that a uvrA mutant was about 20 times more sensitive to BPDE killing and BPDE-induced mutations than was wild-type E. coli. This suggests that BPDE-DNA lesions are removed by an excision repair mechanism similar to that which excises pyrimidine dimers. Although strains carrying either recA or lexA mutations were also more sensitive to BPDE killing, BPDE was not mutagenic in these strains. The recA+ and lexA+ gene products coordinately control the regulation of a set of genes that are expressed in response to DNA-damaging agents (SOS functions). Therefore, our results indicate that in E. coli BPDE is an indirect mutagen that acts through host-mediated functions, i.e., the SOS pathway, in the process of mutation fixation. The possible significance of these findings to carcinogenesis are discussed.
在本研究中，利用在大肠杆菌B/r野生型以及uvrA、recA和lexA突变体中从trp到Trp+的碱基对回复突变的诱导来分析苯并(a)芘-7,8-二氢二醇9,10-环氧化物（BPDE）的诱变机制。将BPDE诱变与两种特征明确的诱变剂的诱变作用进行了比较：甲磺酸乙酯和4-硝基喹啉1-氧化物。我们发现，uvrA突变体对BPDE杀伤和BPDE诱导的突变的敏感性比野生型大肠杆菌高约20倍。这表明BPDE-DNA损伤是通过一种类似于切除嘧啶二聚体的切除修复机制来去除的。尽管携带recA或lexA突变的菌株对BPDE杀伤也更敏感，但BPDE在这些菌株中不具有诱变性。recA+和lexA+基因产物协同控制一组响应DNA损伤剂而表达的基因的调控（SOS功能）。因此，我们的结果表明，在大肠杆菌中，BPDE是一种间接诱变剂，在突变固定过程中通过宿主介导的功能，即SOS途径发挥作用。讨论了这些发现对致癌作用的可能意义。
