SINGLET OXYGEN INDUCES PREDOMINANTLY G TO T TRANSVERSIONS ON A SINGLE-STRANDED SHUTTLE VECTOR REPLICATED IN MONKEY CELLS

To elucidate the mechanisms of mutagenesis by singlet oxygen DNA damag e in mammalian cells, a SV40-derived single-stranded shuttle vector wa s exposed to the water soluble endoperoxide 3,3'-(1,4-naphthylidene) d ipropionate (NDPO2). The damaged vector was transfected into monkey CO S7 cells and the plasmid progeny exhibited up to 10 fold increase on t he mutation frequency in the supF target gene, when compared to untrea ted vector. The sequence in the supF locus of such mutants revealed th at singlet oxygen-induced mutagenesis in single-stranded vector is sig nificantly different from spontaneous mutagenesis. Among the base subs titutions, most of the mutations involved deoxyguanosines, being G to T transversions the predominant type of change. The data indicate that mutagenesis by singlet oxygen in mammalian cells may be generated by an error prone bypass of damaged deoxyguanosines at the template DNA.