In vitro short-term testing systems as prescreens for potential carcinogens: simultaneous detection of sister chromatid exchanges and mutation response in a cell-mediated assay with V79 cells.

Sister chromatid exchange (SCE) is recognized as a sensitive indicator of genetic damage, and this has led numerous investigators to suggest that the analysis of SCE can provide a useful step toward the identification of environmental mutagens and/or carcinogens. To explore this approach, we measured SCE induction in V79 Chinese hamster lung cells and the frequency of mutation to 6-thioguanine resistance at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus in a cell-mediated mutation assay. Karyotypic analysis of V79 cells showed a stable modal chromosome number of 22 and an XY chromosome complement. When exposed to the procarcinogen 7,12-dimethylbenz[a]anthracene (DMBA) at marginally cytotoxic dose levels of 1.0, 0.5 and 0.25 microM (2.6, 1.3 and 0.65 micrograms/ml), SCE frequencies were highest within the first 24 h of activation with rat or hamster hepatocytes, showed somewhat lower values after 48 h of activation, and, following withdrawal of the chemical, declined to background levels during the period of expression. While this decline may involve several factors, the possibility is not excluded that DNA repair can contribute to the progressive elimination of SCE. The induction of SCE in V79 cells appeared unrelated to the expression of single-point mutation at the HGPRT locus. These findings demonstrate the advantage of multiple endpoint analysis which enabled cytotoxicity, mutagenicity and conditions optimal for the induction of SCE to be determined concurrently in a hepatocyte-mediated assay with V79 cells.