Effects of carcinogenic agents upon different mechanisms for intragenic recombination in mammalian cells
Effects of carcinogenic agents upon different mechanisms for intragenic recombination in mammalian cells
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DOI：
10.1093/carcin/19.6.973
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发表时间：
1998-06-01
期刊：
影响因子：
4.7
通讯作者：
Jenssen, D
中科院分区：
文献类型：
--
作者：
Helleday, T;Arnaudeau, C;Jenssen, D
已知越来越多的致癌物影响哺乳动物细胞中的基因重组，从而干扰致癌过程。为了筛选化学和物理试剂的重组效应，已经开发了多种利用哺乳动物细胞的体外测定系统，然而，潜在致癌物的效应在这些不同的系统中不同。为了进一步研究这一现象，我们采用了两种不同的测定方法，涉及哺乳动物细胞中的自发复制突变体，其响应于同源或非同源重组。研究了四种致癌物，即Aroclor 1221，苯，甲基甲磺酸盐（MMS）和硫脲，以及γ-和UV-照射，除硫脲外，所有这些因素都导致同源重组频率升高，另一方面，只有紫外线照射影响非同源重组率，这些结果表明，底物长度和/或重组机制可能会影响哺乳动物成纤维细胞的致癌因素的重组反应。因此，致癌物的重组效应的程序应考虑哺乳动物细胞中发生的不同重组途径。
A growing body of carcinogens are known to affect genetic recombination in mammalian cells and to thereby interfere with the process of carcinogenesis, In order to screen for recombinogenic effects of chemical and physical agents a variety of in vitro assay systems utilizing mammalian cells have been developed, However, the effects of potential carcinogens differ in these different systems. In order to investigate this phenomenon further, we have employed two different assay procedures, involving spontaneous duplication mutants in mammalian cells, which respond to homologous or non-homologous recombination, Four carcinogens were investigated, i.e. Aroclor 1221, benzene, methylmethanesulphonate (MMS) and thiourea, as were gamma- and UV-irradiation, With the exception of thiourea all of these factors resulted in elevated frequencies of homologous recombination, On the other hand, only UV-irradiation affected the rate of non-homologous recombination, These results indicate that substrate length and/or the recombination mechanism may influence the recombinogenic response of mammalian fibroblasts to carcinogenic factors. Thus, procedures for recombinogenic effects of carcinogens should consider the different pathways of recombination occurring in mammalian cells.