Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarettesmoke-related lipophilic DNA adduct formation. Female Sprague- Dawley ratswere exposed daily to sidestream cigarette smoke in a whole- body exposurechamber 6 h/day for 4 consecutive weeks. One group of rats was maintainedon control diet while another group received the same diet supplementedwith either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz,starting 1 week prior to initiation of smoke exposure until the end of theexperiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5predominated in both the lung and the heart while adduct nos 3 and 2predominated in the trachea and bladder, respectively. Quantitativeanalysis revealed that the total adduct level was the highest in lungs(270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides)and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraztreatment reduced the adduct levels in lungs and bladder by >60%, whilethe reduction in lungs in the low-dose group was approximately 35%. Intrachea, the effect of low and high dietary oltipraz on smoke DNA adductionwas equivocal, while smoke-related DNA adducts in the heart were minimallyinhibited by high-dose oltipraz. In a repeat experiment that employed a3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found toinhibit the formation of DNA adducts in rat lungs and trachea by 80 and65%, respectively. These data clearly demonstrate a high efficacy ofoltipraz in inhibiting the formation of cigarette smoke-induced DNA adductsin the target tissues.