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

Jamal M. Arif, C. Gary Gairola, Howard P. Glauert, Gary J. Kelloff, Ronald A. Lubet, Ramesh C. Gupta

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague-Dawley rats were exposed daily to sidestream cigarette smoke in a whole-body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same 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 exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270 ± 68 adducts/1010 nucleotides), followed by trachea (196 ± 48 adducts/1010 nucleotides), heart (141 ± 22 adducts/1010 nucleotides) and bladder (85 ± 16 adducts/1010 nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by > 60%, while the reduction in lungs in the low-dose group was ~35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.

Original languageEnglish
Pages (from-to)1515-1517
Number of pages3
Issue number8
StatePublished - Aug 1998

ASJC Scopus subject areas

  • Cancer Research


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