Involvement of antipain-sensitive protease activity in suppression of UV-mutagenicity by human interferon-alpha.

To study the relationship between the transient elevation of protease activity and hypomutability observed in hypermutable human RSa cells pretreated with human interferon (HuIFN)-alpha and then irradiated with far-ultraviolet light (UV), protease inhibitors capable of specifically inhibiting the activity were investigated. Of ten inhibitors tested, antipain showed the greatest inhibitory effect. Antipain also prevented the suppression of UV-mutagenicity by HuIFN-alpha in RSa and xeroderma pigmentosum-derived fibroblast cells, as shown by culturing cells in medium containing antipain immediately after UV exposure and evaluating the generation of clones resistant to ouabain- or 6-thioguanine-mediated cytotoxicity. Thus, an antipain-sensitive protease may be involved in the hypomutability induced by HuIFN-alpha.