Concentration- and time-dependent formation of DNA adducts in lungs of rats exposed to diesel exhaust.
Diesel exhaust (DE) is a pulmonary carcinogen in rodents. Previous studies have demonstrated that following exposure of rats to high concentrations (10 mg soot/m3) of DE, DNA adducts can be measured in lung tissue. The purpose of the present study was to characterize the kinetics of formation and persistence of lung DNA adducts after a 12-week exposure to DE and to determine the effect of exposure concentration on adduct formation. Rats were exposed for 7 h/day, 5 days/week, for up to 12 weeks, to filtered air (controls) or to diluted DE (0.35-10 mg soot/m3). DNA from lungs of rats was analyzed for the presence of DNA adducts by the 32P-postlabeling method. Levels of DNA adducts in lungs of rats exposed to the different exhaust concentrations were similar, and were about twice control values (approximately 14 vs. 7 adducts/10(9) bases). DNA adduct levels in lungs of control rats remained relatively constant throughout the 12-week exposure period. In contrast, lung DNA adduct levels in rats exposed to DE soot accumulated slowly during the 12-week exposure, and were highest at the end of exposure. DNA adduct levels declined rapidly after the termination of exposure. Because adduct levels in lungs were similar at all concentrations examined and the finding that adducts were increased in rats at an exposure level that does not significantly increase tumor incidence (0.35 mg soot/m3), it is likely that factors in addition to lung DNA adduct formation must be involved in DE-induced carcinogenicity. We concluded that the formation of lung DNA adducts by metabolites of soot-associated organic compounds may be only one step in the initiation of DE-induced pulmonary carcinogenesis.
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185.
J A
JA
Bond
J L
JL
Mauderly
R K
RK
Wolff
D000280:Administration, Inhalation; D000818:Animals; D001564:Benzo(a)pyrene / Q000032:analysis; D002274:Carcinogens, Environmental / Q000032:analysis*; D002855:Chromatography, Thin Layer; D003043:Cocarcinogenesis; D004247:DNA / Q000032:analysis*; D018736:DNA Adducts; D004249:DNA Damage; D008168:Lung / Q000032:analysis / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D001335:Vehicle Emissions / Q000633:toxicity*
D002274:Carcinogens, Environmental; D018736:DNA Adducts; D001335:Vehicle Emissions; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D004247:DNA