Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz.
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.
Arif
J M
JM
Department of Preventive Medicine and Environmental Health, University of Kentucky, Lexington 40536, USA.
Gairola
C G
CG
Glauert
H P
HP
Kelloff
G J
GJ
Lubet
R A
RA
Gupta
R C
RC
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018736:DNA Adducts / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D008168:Lung / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013871:Thiones; D013876:Thiophenes; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014132:Trachea / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism
D016588:Anticarcinogenic Agents; D018736:DNA Adducts; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; D014028:Tobacco Smoke Pollution; C026209:oltipraz