Suppression of cylotoxic effect of mitomycin-C by superoxide dismutase in Fanconi's anemia and dyskeratosis congenita fibroblasts

Abstract

Survival curves were determined for several human diploid fibroblast strains treated with mitomycin-C (MMC) with or without concomitant incubation with superoxide dismutase (SOD). These included cells from patients with Fanconi''s anemia (FA), dyskeratosis congenita (DC) a disorder related to FA, Gardner''s syndrome (GS) and xeroderma pigmentosum group C (XPC). Incubation with SOD had no effect on MMC-induced cytotoxicity in the 2 normal cell strains, XPC or GS. Although GM2053 (FA) and 2 DC strains showed intermediate sensitivity to killing by MMC similar to XPC and GS, the survival of these cell strains was increased approximately 2-4 times after 0.5 .mu.g/ml of MMC by concomitant treatment with SOD. Survival of the most MMC sensitive cell strain GM1309 (FA) was sharply increased by adding SOD; survival was enhanced about 15-fold after treatment with 0.1 .mu.g/ml of MMC. SOD induced no enhancement of survival in MMC treated normal cells at survival levels down to nearby 10-3. The hypersensitivity to MMC cytotoxicity in FA and DC cells may involve among other factors a deficiency in the inactivation of certain free radical intermediates.