INHIBITION OF CIGARETTE SMOKE-RELATED LIPOPHILIC DNA-ADDUCTS IN RAT-TISSUES BY DIETARY OLTIPRAZ

The present study investigated the effects of dietary oltipraz on ciga rette smoke-related lipophilic DNA adduct formation. Female Sprague-Da wley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of ra ts was maintained on control diet while another group received the sam e diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m. ) dose of oltipraz, starting 1 week prior to initiation of smoke expos ure until the end of the experiment. Analysis of lipophilic DNA adduct s by the nuclease pi-mediated P-32-post-labeling showed up to five smo ke-related adducts, Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladde r, respectively, Quantitative analysis revealed that the total adduct level was the highest in lungs (270 +/- 68 adducts/10(10) nucleotides) , followed by trachea (196 +/- 48 adducts/10(10) nucleotides), heart ( 141 +/- 22 adducts/10(10) nucleotides) and bladder (85 +/-. 16 adducts /10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in t he low-dose group was similar to 35%, In trachea, the effect of low an d high dietary oltipraz on smoke DNA adduction was equivocal, while sm oke-related DNA adducts in the heart were minimally inhibited by high- dose oltipraz, In a repeat experiment that employed a 3-fold lower dos e of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the f ormation of DNA adducts in rat lungs and trachea by 80 and 65%, respec tively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.