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FORMATION OF 8-OXO-2'-DEOXYGUANOSINE, AN OXIDATIVE ADDUCT IN THE LUNG DNA OF RATS FOLLOWING SUBCHRONIC INHALATION OF CARBON BLACK
Citation:
Prahalad, A. K., J Inmon, R. Gelein, A. Elder, G. Oberdorster, AND J Gallagher. FORMATION OF 8-OXO-2'-DEOXYGUANOSINE, AN OXIDATIVE ADDUCT IN THE LUNG DNA OF RATS FOLLOWING SUBCHRONIC INHALATION OF CARBON BLACK. Presented at American Association for Cancer Research Annual Meeting, New Orleans, LA, March 24-28, 2001.
Description:
Chronic inhalation of carbon black (CB) can produce carcinomas in rat lungs. The mechanisms underlying this response are uncertain. However, it has been postulated that chronic inflammation and cell proliferation may play a role in the development of tumors after high dose, long-term contact of the particles with lung epithelial cells. In this investigation, we analyzed for a known mutagenic lesion 8-oxo-2'-deoxyguanosine (8-oxo-dG) in the lung DNA of rats following subchronic inhalation of CB. Briefly, female Fischer 344 rats were exposed for 6 hr/day, 5 days/week for up to 13 weeks to 1, 7, and 50 mg/m3 CB and the formation of 8-oxo-dG in the lung DNA was assessed using reverse phase HPLC system coupled with UV electrochemical (EC) detection after 13 weeks of exposure and a 11 month recovery period in clean air. Lung burdens of CB were also determined at the designated time points. The results indicate that lung particle overload was achieved after exposure to 7 and 50 mg/m3 but not at 1 mg/m3. Consistent with these results, a significant increase in 8-oxo-dG induction was observed following 13 weeks of exposure to 50 mg/m3 CB which persisted through an 11 month recovery period. A significant elevation of 8-oxo-dG when compared to control animals for the 7 mg/m3 exposure group was detected at the 11 month recovery period but not with the 13 week exposure group, suggesting that high dose inhalation and lung deposition of CB induces continued perturbation within pulmonary epithelial cells which persists and overwhelms the repair process of this oxidative adduct. Subchronic inhalation of 1 mg/m3 CB did not elicit any detectable change in the 8-oxo-dG level relative to control group. Our current findings that prolonged exposure to CB can promote oxidative DNA damage is in line with the hypothesis that inflammatory cell-derived oxidants and cell proliferation may play a role in the pathogenesis of rat lung tumors following long-term, high dose exposure to CB in rats. [This research was in part supported by the International Carbon Black Association (ICBA) and by the EPA/UNC Toxicology Research program (CT902908). This abstract does not necessarily reflect U.S. EPA policy].