Analysis of human cells with super-sensitivity to mutagenicity

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A human transformed cell line, RSa, has unusually high sensitivity to UV-mutagenicity (1 mutant per 10<@D12@>D2 survivals). The high sensitivity was found to be due to abnormal metabolism of plasminogen activator-like protease activities, as follows.1. Mutation frequencies of UV^r-1, a UV-resistant variant of a human RSa cell line, were decreased ones. UV^r-1 cells have much the same levels of DNA-repair replication synthesis as those of RSa cells, and thus may acquire another error-free repair functions.In UV-irradiated UV^r-1 cells levels of plasminogen activator-like protease activities increased, whereas in the irradiated RSA cells those of the activities did not. Therefore, there may exist factors which have the protease activities and can regulate mutation.2. Mutation frequencies of-RSa cells, treated with interferon prior to UV irradiation, decreased, but again increased cycloheximide treatment after irradiation. In interferon-pretreated RSa cells levels of protease activities increased immidiately after irradiation, but decreased by the cycloheximide treatment.3. The above-described interferon and cycloheximide effects could be detected in fibroblasts of xeroderma pigmentosum patients with high frequencies of mutation.