TY - JOUR
T1 - Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz
AU - Arif, Jamal M.
AU - Gairola, C. Gary
AU - Glauert, Howard P.
AU - Kelloff, Gary J.
AU - Lubet, Ronald A.
AU - Gupta, Ramesh C.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/8
Y1 - 1998/8
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/19.8.1515
DO - 10.1093/carcin/19.8.1515
M3 - Article
C2 - 9744551
AN - SCOPUS:0031657288
SN - 0143-3334
VL - 19
SP - 1515
EP - 1517
JO - Carcinogenesis
JF - Carcinogenesis
IS - 8
ER -