UV-induced mutations affecting codon 12 of the K- ras gene are suppressed by interferon-α in human RSa cells

Abstract

K- ras gene sequences mutant at codon 12 were recovered following differential dot-blot hybridization of genomic DNA from human RSa cells up to 12 days after the cells had been irradiated with far-UV (principally 254 nm). By contrast, no mutant codon 12 sequences were recovered from cells which had been treated with 50 IU/ml human interferon (HuIFN)-α for 24 h prior to their UV exposure. HuIFN-α treatment in combination with anti-HuIFN-α antibody did not lead to the loss of mutant sequences. However, culture of interferon-pretreated cells with medium containing the protease inhibitor antipain (0.01 mM) for 6 h immediately after UV irradiation led to the recovery of mutant codon 12 sequences. Thus, while treatment with HuIFN-α appeared to prevent any UV-induced mutations affecting codon 12 of the K- ras gene from being recovered, the putative antipain-sensitive protease responsible for this suppressive affect appeared to be significantly affected by the protease inhibitor antipain.