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

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 grop C (XPC). Incubation with SOD had no effect on MMC-induced cytotoxicity in the two normal cell strains, XPC or GS. Although GM2053 (FA) and two 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 microgram/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 microgram/ml of MMC. SOD induced no enhancement of survival in MMC treated normal cells at survival levels down to nearly 10(-3). We propose that the hypersensitivity to MMC cytoxicity in FA and DC cells may involve among other factors a deficiency in the inactivation of certain free radical intermediates.