[Mutagenesis under the influence of simian virus 40 (SV40). II. Induct?ION OF MUTATIONS RESULTING IN RESISTANCE TO PURINE BASE ANALOGS IN HUMAN AND Chinese hamster cells].
Induction of gene mutations by SV40 was studied in aneuploid human and Chinese hamster cell lines. It is shown that SV40 penetrates into the cells studied and induces the T-antigen synthesis. The efficiency of the infection in Chinese hamster cells was tested additionally by the ability of infected cells to form colonies in the medium lacking serum growth factor. The maximal number of colony-forming cells was detected 24 hours after the infection. By culturing cells in factor-free medium a Chinese hamster cell subline was isolated, which proved to synthetize T-antigen within 60 days after the virus treatment. This is regarded as an indirect proof of the integration of viral genome into the cell genome. The increased frequency of mutants resistant to 60 mkg/ml of 8-azaguanine (human cells) and to 15 mkg/ml of 6-mercaptopurine (hamster cells) was observed on the 1--4th days following the infection. The analysis of the results of all experiments taken together revealed that the induction is highly significant according to Wilcoxon (greater than 0.99). The resistance of the isolated clones proved to be stable after the prolonged culturing under non-selective conditions. It is suggested that viral genome integration, gene mutations and chromosome aberrations may have common molecular mechanisms. The role of gene mutations in virus-induced carcinogensis and tumour progression is discussed.