Mechanism(s) of turmeric-mediated protective effects against benzo(a)pyrene-derived DNA adducts.
The effects of turmeric feeding before and after benzo(a)pyrene [B(a)P] exposure on the levels of B(a)P-derived DNA adducts were studied in tissues of Swiss mice employing (32)P-postlabelling analysis. A reduction in the levels of B(a)P-derived DNA adducts in liver, lung, and forestomach was observed in animals pre-treated with 0.2 or 1% turmeric diet and exposed to B(a)P by oral intubation when compared to animals receiving standard laboratory diet and B(a)P. The observed decrease was not due to dilution caused by nascent DNA synthesis. Comparative evaluation of levels of B(a)P-derived DNA adducts in tissues of animals shifted to 0.2 or 1% turmeric diet after 24 h of oral intubation of B(a)P with those continued on standard laboratory diet did not suggest enhanced disappearance/repair of B(a)P-derived DNA adducts due to exposure to turmeric. Further, pre-treatment of mice with 1% turmeric diet significantly reduced the B(a)P-induced increase in activity of cytochrome P450 (CYP450) isozymes CYP 1A1 and 1A2 in liver, lung, and forestomach of mice. In addition, hepatic glutathione S-transferase (GST) was found to be elevated in turmeric pre-treated mice. Thus turmeric-mediated decrease in induction of phase-I enzymes in liver, lung, and forestomach of mice and enhancement of hepatic GST appear to play an important role in reducing the B(a)P-induced DNA damage in target and non-target tissues.
Thapliyal
Rachana
R
Carcinogenesis Division, Cancer Research Institute, Tata Memorial Centre, Parel, 400 012, Mumbai, India.
Deshpande
Shailesh S
SS
Maru
Girish B
GB
D000704:Analysis of Variance; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000493:pharmacokinetics / Q000633:toxicity*; D030024:Curcuma / Q000502:physiology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D018736:DNA Adducts / Q000493:pharmacokinetics / Q000633:toxicity*; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism; D013270:Stomach / Q000201:enzymology; D014018:Tissue Distribution
D016588:Anticarcinogenic Agents; D002274:Carcinogens, Environmental; D018736:DNA Adducts; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase