Cigarette Tar Promotes Neutrophil-Induced DNA Damage in Cultured Lung Cells

Abstract

We have investigated the ability of aqueous cigarette tar extracts to promote human polymorphonuclear leukocyte (PMNL)- and hydrogen peroxide (H 2O 2)-induced DNA single-strand breaks (DNA-SSB) in cultured human lung cells. Tar extract itself did not cause any DNA-SSB formation, whereas PMNL (activated with phorbol myristate acetate (PMA)) and H 2O 2 both caused a small but significant DNA-SSB formation on their own. On the other hand, if cells were first treated with tar extract and then exposed to PMA-activated PMNL or H 2O 2, the DNA-SSB formation increased considerably. Pretreatment with iron-loaded tar extracts caused a greater increase after PMNL exposure than pretreatment with regular tar extracts. No DNA-SSB formation was found if catalase was present during the PMNL exposure, indicating that H 2O 2 was important for the PMNL-induced DNA damage. These findings suggest that cigarette tar promotes neutrophil-induced DNA damage in human lung cells and that this effect can be further potentiated by iron. This can be of importance in explaining the carcinogenic effects of cigarette smoking and the increased risk of lung cancer among asbestos workers and iron miners who smoke.