Human tumor cell strains both unable to repair O6-methylguanine and hypersensitive to killing by human alpha and beta interferons.

Abstract

Human brain tumor cell strains were previously found by others to be sensitive to growth inhibition by human interferon-beta (HuIFN-beta). We noticed that the sensitive strains were some that we had found deficient in the repair of O6-methylguanine (O6MeG), a characteristic of 20% of the human tumor cell strains we have studied. We confirmed this sensitivity to HuIFN-beta, and have further shown that human brain tumor cells which repair O6MeG are resistant to the growth inhibitory effects of HuIFN-beta. In addition, treatment with HuIFN-alpha or HuIFN-beta resulted in more killing (reproductive inactivation) of six human tumor cell strains deficient in repairing O6-methylguanine in DNA than did such treatment of six strains of cells proficient in such repair. Further, we found two human lines, altered to become O6MeG repair deficient after establishment of the primary tumor cell culture, that were resistant to interferon. IFN treatment produced no DNA damage detectable by either chemical or biological assays. It is suggested that the genes responsible for resistance to IFN treatment and to agents that produce O6MeG are often coordinately shut down.