Relationship of X-ray and mitomycin-C (MMC) induced cytotoxicity to intracellular superoxide dismutase (SOD) content

SOD levels and complete survival curves following treatment of density-inhibited cultures were measured in human diploid fibroblasts isolated from patients with monosomy-21 (GM230), Trisomy-21 (GM2067, GM4823, TC106, TC108, TC161), FA (6M1309); dykeratosis congenita (DC) (GM1774, GM4646) and two normal (GM730, AG1522). Monosomy-21 (SOD content 60% of normal), FA (SOD 60%) and DC were slightly hypersensitive to x-rays (D/sub o/ 100 rads vs. normal D/sub o/ 130-140 rads). Trisomy-21 (SOD 150%) also showed increased sensitivity (D/sub o/ 80-100 rads) but was less sensitive that AT cells (D/sub o/ 40-50 rads). Incubation with DMSO during x-irradiation greatly enhanced survival of Trisomy-21 cells. FA was extremely hypersensitive and monosomy-21 and DC moderately hypersensitive to MMC, whereas Trisomy-21 was close to normal. The authors hypothesize that the cytotoxicity of MMC relates at least in part of O/sub 2/- production, rendering cells with reduced intracellular SOD content hypersensitive to this agent. X-ray-induced cytotoxicity, however, results from OH radicals which are important products in the presence or absence of SOD