RESPONSES OF ALVEOLAR MACROPHAGES AND EPITHELIAL TYPE-II CELLS TO OXIDATIVE DNA-DAMAGE CAUSED BY PARAQUAT

Because lung cells are inevitably exposed to chemicals, drugs and mine ral particles, they are appropriate target cells for investigating eff ects of environmental toxins. We have studied alveolar macrophages and epithelial type ZI pneumocytes freshly isolated from the rat lung, us ing the comet assay to detect DNA damage (strand breaks and oxidized b ases) in individual cells after treatment with the pesticide paraquat. The background level of strand breaks is five times higher in freshly isolated pneumocytes than in alveolar macrophages, This difference re mains even after 48 h of in vitro culture and therefore probably does not reflect trauma suffered during isolation. In contrast, endogenous formamidopyrimidine glycosylase-and endonuclease III-sensitive sites, which are specific indicators of oxidative damage, are present in fres hly isolated alveolar macrophages but not in pneumocytes, reflecting t he high metabolic activity of macrophages and their defensive role, Bo th cell types are exquisitely sensitive to strand breakage by paraquat . In addition, specific base oxidation is detected after 24 h of treat ment with paraquat, especially in alveolar macrophages. Susceptibility to DNA damage, rather than lipid peroxidation, is likely to be the ca use of paraquat-induced death in these cells. The relatively high leve l of endogenous damage in pneumocytes suggests that these cells are in efficient at DNA repair, which would be consistent with their probable role as the principal progenitors of lung cancer.