1,N(2)-propanodeoxyguanosine adduct formation in aortic DNA following inhalation of acrolein.
Recent reports indicate that many of the cytotoxic and health-threatening components of environmental tobacco smoke (ETS) reside in the vapor phase of the smoke. We have reported previously that inhalation of 1,3-butadiene, a prominent vapor phase component of ETS, accelerates arteriosclerotic plaque development in cockerels. In this study we asked whether inhaled acrolein, a reactive aldehyde that is also a prominent vapor-phase component of ETS, damages artery-wall DNA and accelerates plaque development. Cockerels inhaled 0, 1, or 10 ppm acrolein mixed with HEPA-filtered air for 6 hr. Half were killed immediately (day 1 group) for detection of the stable, premutagenic 1,N(2)-propanodeoxyguanosine acrolein adduct (AdG3) in aortic DNA via a (32)P-postlabeling/HPLC method, and half were killed after 10 days (day 10 group) for indirect assessment of adduct repair. In the day 1 group, acrolein-DNA adducts were 5 times higher in the 1 and 10 ppm groups than in HEPA-filtered air controls. However, in the day 10 group, adduct levels in the 1 and 10 ppm acrolein groups were reduced to the control adduct level. For the plaque studies, cockerels inhaled 1 ppm acrolein (6 hr/day, 8 weeks), mixed with the same HEPA-filtered air inhaled by controls. Plaque development was measured blind by computerized morphometry. Unlike butadiene inhalation, acrolein inhalation did not accelerate plaque development. Thus, even though repeated exposure to acrolein alone has no effect on plaque size under the exposure conditions described here, a single, brief inhalation exposure to acrolein elicits repairable DNA damage to the artery wall. These results suggest that frequent exposure to ETS may lead to persistent artery-wall DNA damage and thus provide sites on which other ETS plaque accelerants can act.
Penn
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Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, South Stadium Road, Baton Rouge, LA 70803, USA. apenn@mail.vetmed.lsu.edu
Nath
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Pan
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Chen
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Widmer
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Henk
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Chung
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D000171:Acrolein / Q000494:pharmacology*; D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D003324:Coronary Artery Disease / Q000209:etiology; D018736:DNA Adducts / Q000032:analysis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis*; D009153:Mutagens / Q000032:analysis*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects
C090855:1,N(2)-(1,3-propano)-2'-deoxyguanosine; D000393:Air Pollutants; D018736:DNA Adducts; D009153:Mutagens; D014028:Tobacco Smoke Pollution; D000171:Acrolein; D003849:Deoxyguanosine