Induction of sister chromatid exchanges in cultured adult rat hepatocytes by directly and indirectly acting mutagens/carcinogens.
Primary cultures of adult rat hepatocytes were tested for their suitability to assess sister chromatid exchange (SCE)-inducing DNA damage produced by both directly and indirectly acting mutagens/carcinogens. Compared to other genotoxicity assay systems which utilize the metabolizing activity of liver microsomes, this system is at least 1-2 orders of magnitude more sensitive. The approximate drug concentrations leading to a doubling of control SCE levels were 2.5 X 10(-4) M for cyclophosphamide, 4.5 X 10(-5) M for dimethylnitrosamine, 2.5 X 10(-6) M for N-methyl-N-nitro-N-nitrosoguanidine, 2 X 10(-10) M for aflatoxin B1 (AFB1) and 30 mJ for u.v. The most potent inducer of SCE proved to be AFB1, leading to a significantly elevated level of exchanges at a concentration of 10(-12) M. The increased background SCE levels observed (0.75 SCE/chromosome) appears to reflect the sensitivity of hepatocytes to SCE-inducing DNA damage resulting from the dietary intake of mutagenic/carcinogenic compounds. In view of the high sensitivity and versatility of this genotoxicity assay system, it will be of use for the detection of the low levels of mutagenic/carcinogenic compounds found in the environment.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000494:pharmacology; D004128:Dimethylnitrosamine / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000187:drug effects*; D009153:Mutagens / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012854:Sister Chromatid Exchange
D000348:Aflatoxins; D002273:Carcinogens; D009153:Mutagens; D003520:Cyclophosphamide; D016604:Aflatoxin B1; D004128:Dimethylnitrosamine