Induction of DNA strand breaks by trihalomethanes in primary human lung epithelial cells.

Trihalomethanes (THMs) are disinfection by-products and suspected human carcinogens present in chlorinated drinking water. Previous studies have shown that many THMs induce sister chromatid exchanges and DNA strand breaks in human peripheral blood lymphocytes in vitro. Exposure to THMs occurs through oral, dermal, or inhalation routes, with the lung being a target of exposure by the latter route, although not a target for rodent carcinogenicity. Thus, to examine the genotoxicity of THMs in this tissue, we used the comet assay to examine the DNA damaging ability of five THMs in primary human lung epithelial cells. Cells were collected by scraping the large airways of four volunteers with a cytology brush and then passaging the cells no more than three times in order to have sufficient numbers for the experiments. Cells were exposed for 3h to 10, 100, or 1000 microM CHCl(3), CHCl(2)Br, CHClBr(2), or CHBr(3); CH(2)Cl(2) was also used as a model dihalomethane for comparison to the THMs. The compounds ranked as follows for DNA damaging ability: CHCl(2)Br>CHBr(3)>CHCl(3) approximately equal CH(2)Cl(2); CHClBr(2) was negative. Considerable inter-individual variation was observed. For example, CHCl(3) was genotoxic in only two subjects, and the interaction between dose and donor was highly significant (P