OXIDATIVE DAMAGE IN TISSUES OF RATS EXPOSED TO CIGARETTE-SMOKE

Cigarette smoke is known to contain high concentrations of free radica ls and oxidants. To examine the oxidative effect of cigarette smoking, we subjected rats to inhalation of cigarette smoke, and measured cell ular free glutathione, the degree of protein S-thiolation, and 8-oxo-2 'deoxyguanosine (oxo(8)dG) in DNA. Inhalation of the cigarette smoke f or 30 days, three times a day, resulted in a significant decrease of t he total free glutathione contents in tissues, especially in the lung. Elevated levels of oxidized glutathione and protein S-thiolation were observed in the lung but not in other tissues. Increased contents of oxo(8)dG in DNA were found in all tissues analyzed. When rats were tre ated with buthionine sulfoximine (BSO, 80 mg/kg/day) to deplete glutat hione, the oxidative effect of cigarette smoking was greatly potentiat ed. The effect of glutathione depletion was most evident in the lung. Cigarette smoking for only 7 days resulted in extreme depletion of the glutathione both in the lungs and in the liver of BSO-treated rats. F urthermore, oxo(8)dG in DNA increased markedly, especially in lung. Th e results verified that the lung is a primary target of cigarette smok e-induced oxidative damage, and cigarette smoke exerts its oxidative e ffects on the rest of the entire organs eventually. Our results indica te that glutathione plays crucial roles in protecting proteins and DNA from oxidation caused by cigarette smoking. (C) 1998 Elsevier Science Inc.