Error-prone replication of ultraviolet-irradiated simian virus 40 in carcinogen-treated monkey kidney cells.

To analyze the molecular mechanism of mutagenesis in carcinogen-treated mammalian cells, we developed a model system composed of various simian virus 40 (SV40) mutants as a biological probe to detect inducible DNA repair and mutagenesis in carcinogen-treated monkey kidney cells (CV1-P). Results have shown that treatment of cells with UV-light, acetoxy-acetyl-aminofluorene, or mitomycin C, increases the mutagenesis of UV-irradiated SV40 ts mutant measured as a reversion frequency from a thermosensitive phenotype toward a thermoresistant phenotype. This increased mutagenesis is not observed in the case of undamaged virus indicating that we are looking at targeted mutagenesis. The molecular analysis of several revertant genomes indicates that some DNA rearrangements may occur in the revertant genomes but in some cases the reversion site is a single basepair substitution located at positions different from the original thermosensitive mutation, which is still present. The general interpretation of our results leads to the conclusion that carcinogen treatment of monkey cells activates some kind of error-prone replication mode able to better replicate UV-damaged templates but leading to a higher level of mutagenesis. This activity may represent a SOS-like function in mammalian cells.