Relationship between sister chromatid exchange and mutagenicity, toxicity and DNA damage

Reciprocal exchanges of DNA in sister chromatids (SCEs) are induced by various carcinogens and mutagens, although the quantitative relationship between the number of mutations and SCEs induced varies among chemicals. Nevertheless, the analysis of SCE production by various agents is often proposed as a sensitive and quantitative assay for genetic damage of the sort leading to mutation and cancer. In V-79 Chinese hamster cells we have been measuring DNA damage by alkaline elution, mutation induction as detected by 6-thioguanine resistance, and cytotoxicity as detected by colony formation for different physical and chemical agents. Some of the agents produced varying forms of DNA damage but undetectable increases in either mutation or toxicity. We report here that some undetectably mutagenic and/or toxic agents produce increases in SCE frequency and that DNA single-stranded breaks, DNA--DNA interstrand cross-links, and DNA--protein cross-links are not necessary for SCE.