PROTECTIVE ROLE OF MANGANESE SUPEROXIDE-DISMUTASE AGAINST CIGARETTE SMOKE-INDUCED CYTOTOXICITY

Free-radical-induced oxidative damage has been implicated as an import ant mechanism responsible for the toxicity of both active and passive smoking. Cigarette smoke contains short- and long-lived radicals and c an stimulate cellular production or highly reactive oxygen species. On e of the antioxidant enzymes that is protective against reactive oxyge n-induced damage is manganese superoxide dismutase (MnSOD), which is l ocated in the mitochondria of mammalian cells. The present study was c onducted to examine the role of oxidative damage in cigarette smoke to xicity. A mouse fibroblast cell line (C3H10T1/2) and its MnSOD-transfe cted, enzymatically active clone, R2 cells, which possessed about five fold greater MnSOD activity, were used to test the cytotoxicity of con densates from mainstream (MS-CSC) and sidestream (SS-CSC) cigarette sm oke. Growth and respiration studies of the two test cell lines showed that the R2 cells grew to a higher cell density and exhibited greater oxygen uptake than the parent cells under normal growth conditions. Bo th smoke condensates were cytotoxic to test cells, but SS-CSC exhibite d slightly greater toxicity, and R2 cells were significantly less susc eptible to SS-CSC toxicity than the parent cells. SS-CSC caused a slig htly greater inhibition of respiratory activity in parent cells than i n R2 cells. These results suggest a significant contribution of oxidat ive damage in SS-CSC cytotoxicity.