Hypomutable potential accompanying interferon-alpha resistance in a human cell line, IFr, derived from...

A human cell line, IFr, established from RSa cells, is a variant with increased resistance to cell proliferation inhibition (CPI) by human interferon (HuIFN)-alpha. 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 10(4) surviving cells after UV (0-12 J/m2), in contrast to 1-53 OuaR mutants per 10(4) 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 previous finding of antipain-sensitive protease induction in UV-irradiated or HuIFN-alpha-treated IFr cells, suggest that antipain-sensitive proteases or cellular functions or both may be involved in not only HuIFN-alpha resistance but also hypomutability of IFr cells.