Hypomutable Potential Accompanying Interferon-α Resistance in a Human Cell Line, IFr, Derived from Interferon-αSensitive and Hypermutable RSa Cells

A human cell line, IFr, established from RSa cells, is a variant with increased resistance to cell proliferation inhibition (CPI) by human interferon (HuIFN)-α. The parent RSa cells are also hypermutable after irradiation with far-ultraviolet light (UV), as assessed by two different methods: cloning efficiency of ouabain-resistant (OuaR) mutants and K-ras codon 12 mutation in genomic DNA identified by polymerase chain reaction (PCR) following differential dot-blot hybridization. In the present study, IFr cells were found to be hypomutable: Less than 1 OuaR mutant per 104 surviving cells after UV (0-12 J/m2), in contrast to 1-53 OuaR mutants per 104 survivors in RSa cells, and no-detectable K-ras codon 12 mutation at any doses tested. However, IFr cells, when cultured with medium containing the protease inhibitor antipain after UV irradiation showed hypermutability to almost the same extent as RSa cells, as determined by both phenotypic and genetic mutation analyses. These results, together with the previo...