Carcinogenesis, Vol 19, 1515-1517, Copyright © 1998 by Oxford University Press
JM Arif, CG Gairola, HP Glauert, GJ Kelloff, RA Lubet and RC Gupta
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/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 the low-dose group was approximately 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.
ARTICLES
Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz
Department of Preventive Medicine and Environmental Health, University of Kentucky, Lexington 40536, USA.
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