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 mineral particles, they are appropriate target cells for investigating effects of environmental toxins. We have studied alveolar macrophages and epithelial type II pneumocytes freshly isolated from the rat lung, using the comet assay to detect DNA damage (strand breaks and oxidized bases) 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 remains 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 freshly isolated alveolar macrophages but not in pneumocytes, reflecting the high metabolic activity of macrophages and their defensive role. Both cell types are exquisitely sensitive to strand breakage by paraquat. In addition, specific base oxidation is detected after 24 h of treatment with paraquat, especially in alveolar macrophages. Susceptibility to DNA damage, rather than lipid peroxidation, is likely to be the cause of paraquat-induced death in these cells. The relatively high level of endogenous damage in pneumocytes suggests that these cells are inefficient at DNA repair, which would be consistent with their probable role as the principal progenitors of lung cancer.
Dusinská
M
M
Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic. dusinska@upkm.sanet.sk
Kovaciková
Z
Z
Vallová
B
B
Collins
A
A
D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006540:Herbicides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D006540:Herbicides; D010269:Paraquat