HYPOMUTABLE POTENTIAL ACCOMPANYING INTERFERON-ALPHA RESISTANCE IN A HUMAN CELL-LINE, IFR, DERIVED FROM INTERFERON-ALPHA-SENSITIVE 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 i nterferon (HuIFN)-alpha. The parent RSa cells are also hypermutable af ter irradiation with far-ultraviolet light (UV), as assessed by two di fferent methods: cloning efficiency of ouabain-resistant (Oua(R)) muta nts and K-ras codon 12 mutation in genomic DNA identified by polymeras e chain reaction (PCR) following differential dot-blot hybridization, In the present study, IFr cells were found to be hypomutable: Less tha n 1 Oua(R) mutant per 10(4) surviving cells after UV (0-12 J/m(2)), in contrast to 1-53 Oua(R) mutants per 10(4) survivors in RSa cells, and no-detectable K-ras codon 12 mutation at any doses tested, However, I Fr cells, when cultured with medium containing the protease inhibitor antipain after UV irradiation showed hypermutability to almost the sam e extent as RSa cells, as determined by both phenotypic and genetic mu tation 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 cellul ar functions or both may be involved in not only HuLFN-alpha resistanc e but also hypomutability of IFr cells.