Action of some retinol derivatives and their provitamins on microsome-catalyzed formation of benzo[a]pyrene-DNA adduct.
Several vitamin A compounds have been tested for their ability to suppress formation of DNA adduct by the carcinogen benzo[a]pyrene (B[a]P) in an in vitro reaction catalyzed by rat liver microsomes. Retinol, retinal, 3-dehydroretinol and 3-hydroxyretinol were found to be effective inhibitors of adduct formation. Certain carotenoids that are precursors of these retinoids also displayed considerable inhibitory capacity. Carotenoids and the 3-substituted retinoids appeared to modulate the DNA adduct formation exclusively through their action on microsomal enzymes, since an effective inhibition in each case was observed on the formation of B[a]P-7,8-diol, a proximate carcinogenic metabolite of B[a]P. Unsubstituted retinoids, on the other hand, had marginal effect on enzymes but were found effective in accelerating inactivation of B[a]P-7,8-diol-9,10-epoxide, the ultimate carcinogenic metabolite that binds to DNA.
Shah
G M
GM
Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Bombay, India.
Goswami
U C
UC
Bhattacharya
R K
RK
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D001682:Biological Availability; D002384:Catalysis; D002417:Cattle; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes / Q000633:toxicity; D004357:Drug Synergism; D008861:Microsomes / Q000187:drug effects*; D014801:Vitamin A / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes; D014815:Vitamins; C056612:benzo(a)pyrene-DNA adduct; D014801:Vitamin A; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene; D004247:DNA