1,N-2-propanodeoxyguanosine adduct formation in aortic DNA following inhalation of acrolein

Recent reports indicate that many of the cytotoxic and health-threatening c omponents 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 plaqu e 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 inh aled 0, 1, or 10 ppm acrolein mixed with HEPA-filtered air for 6 hr. Half w ere killed immediately (day 1 group) for detection of the stable, premutage nic 1,N-2-propanodeoxyguanosine acrolein adduct (AdG3) in aortic DNA via a P-32- postlabeling/HPLC method, and half were killed after 10 days (day 10 group) for indirect assessment of adduct repair. in the day 1 group, acrole in-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 t he plaque studies, cockerels inhaled 1 ppm acrolein (6 hr/day, 8 weeks), mi xed with the same HEPA-filtered air inhaled by controls. Plaque development was measured blind by computerized morphometry. Unlike butadiene inhalatio n, acrolein inhalation did not accelerate plaque development. Thus, even th ough repeated exposure to acrolein alone has no effect on plaque size under the exposure conditions described here, a single, brief inhalation exposur e to acrolein elicits repairable DNA damage to the artery wall. These resul ts suggest that frequent exposure to ETS may lead to persistent artery-wall DNA damage and thus provide sites on which other ETS plaque accelerants ca n act.