Simian virus 40-induced mutagenesis: action of the early viral region

Earlier results have demonstrated a mutagenic activity of simian virus 40 (SV40) in mammalian cells. To analyse this ability further, the effect of SV40 DNA fragments, introduced into Chinese hamster cells, on the frequency of mutations at the hypoxanthine phosphoribosyltransferase locus and other loci was studied. It was found that the mutagenic effect was substantially maintained when the viral genome had been replaced by a fragment comprising the T antigen-coding region and the early promoter-enhancer region; was strongly reduced or abolished when the promoter region including upstream sequences in this fragment had been replaced by the chicken lysozyme gene promoter or both enhancer elements were deleted, and was abolished in an SV40 replication origin-defective mutant in which the structure of the T antigen-binding site II was affected. It may be concluded that SV40-induced mutagenesis depends on the expression of the early region of the genome and on a function involved in specific binding of large T antigen to viral DNA. Since origin-defective mutants of SV40 were reported as being able to transform cells, the functions of transformation and mutation do not seem to correlate.