Induction of DNA damage in cultured human lung cells by tobacco smoke arylamines exposed to ambient levels of ozone.
Ozone (O3) is a powerful oxidizing component of air pollution that may react with other air pollutants before or after inhalation. Because ozonized compounds can be mutagenic to bacteria, we examined whether ambient O3 levels can transform tobacco smoke arylamines into products that are genotoxic to human lung cells. To test this possibility, aqueous solutions of 1-naphthylamine (1-NA) were first exposed to air or O3 in the absence of cells and then used to treat cultured human lung cells, i.e., the diploid fibroblasts CCD-18Lu and the transformed type II epithelial cells A549. DNA single-strand breaks were assayed by DNA alkaline elution. Neither air-exposed 1-NA nor O3-exposed buffer or water were DNA-damaging. However, exposure of 1-NA (15 microM) to O3 (0.1 ppm; 1 h) produced 400 rad equivalents of DNA breaks in either cell type. Although maximal induction of DNA breaks depended upon arylamine concentration, the rates at which DNA-damaging products were formed (activated) and subsequently deactivated depended upon O3 concentration. O3-activated 1-NA was stable for at least 4 h and could damage cellular DNA at 4 degrees C. During ozonization, hydroperoxides were formed at levels equivalent to between 2 and 20 microM of hydrogen peroxide and were eliminated by treatment with catalase. However, failure of catalase and superoxide dismutase to block formation of DNA breaks indicated that neither hydrogen peroxide nor superoxide anions were involved in breaking DNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Kozumbo
W J
WJ
Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill 27599.
Agarwal
S
S
D015057:1-Naphthylamine / Q000494:pharmacology; D000588:Amines / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects*; D004355:Drug Stability; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D010126:Ozone / Q000494:pharmacology*; D010947:Plants, Toxic; D012906:Smoke; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014026:Nicotiana
D000588:Amines; D012906:Smoke; D013481:Superoxides; D010126:Ozone; D015057:1-Naphthylamine; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase