Neutrophils cause oxidative DNA damage in alveolar epithelial cells

Inflammation has been recognized as a contributing factor in the pathogenes is of some cancers. In the lung, inflammation is characterized by an influx of polymorphonuclear leukocytes (PMN) that release a variety of reactive o xygen species (ROS). The aim of the present study was to investigate the di rect effect of PMN on oxidative DNA damage in lung target cells. Therefore, rat alveolar epithelial cells (RLE) were coincubated with PMN or hydrogen peroxide. Known to be correlated with the incidence of cancer, 7-hydro-8-ox o-2'deoxyguanosine (8-oxodG) was used as an effect marker for oxidative dam age. Viability of the RLE, when coincubated with PMN, decreased to 43%, dep endent on the ratio between PMN and RLE. After washing off PMN, 8-oxodG lev els were significantly increased in RLE, but the highest levels were observ ed in the washed off PMN fraction. In addition, to avoid washing off proced ures, immunohistochemical analysis was used to measure the 8-oxodG levels s pecifically in the RLE and similar results were obtained. In addition, inhi bitor experiments showed that antioxidants ameliorated oxidative DNA damage . Our data provide evidence that ROS released by PMN as well as H2O2, cause oxidative DNA damage in epithelial cells. (C) 1999 Elsevier Science Inc.