Effects of carcinogenic agents upon different mechanisms for intragenic recombination in mammalian cells.
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.
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Sweden. helleday@genetics.su.se
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Helleday
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Arnaudeau
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Jenssen
D000818:Animals; D015139:Blotting, Southern; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D011995:Recombination, Genetic / Q000187:drug effects* / Q000528:radiation effects; D012854:Sister Chromatid Exchange
D002273:Carcinogens; D007041:Hypoxanthine Phosphoribosyltransferase