Induction of sister chromatid exchanges in cultured adult rat hepatocytes by directly and indirectly acting mutagens/carcinogens

Abstract

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 .times. 10-4 M for cyclophosphamide, 4.5 .times. 10-5 M for dimethylnitrosamine, 2.5 .times. 10-6 M for N-methyl-N-nitro-N-nitrosoguanidine, 2 .times. 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.