Effect of butylated hydroxyanisole, alpha-angelica lactone, and beta-naphthoflavone on benzo(alpha)pyrene:DNA adduct formation in vivo in the forestomach, lung, and liver of mice.
The effects of alpha-angelica lactone (alpha-AL), butylated hydroxyanisole (BHA), and beta-naphthoflavone (beta-NF) on the amount of benzo(alpha)pyrene (BP) metabolite:DNA adducts formed in the forestomach, lung, and liver of ICR/Ha mice were investigated 48 hr after p.o. administration of BP. BP was administered to mice in amounts known to result in BP-induced neoplasia in certain tissues. Analysis of deoxyribonucleosides by high-pressure liquid chromatography showed that several BP metabolite:DNA adducts were formed in each tissue examined. The major identified adduct in each tissue cochromatographed with the (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(alpha)pyrene (BPDEI):deoxyguanosine adduct. The (+/-)-7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo(alpha)pyrene (BPDEII):deoxyguanosine adduct was detected in each of the tissues. As a percentage of total DNA-associated radioactivity, the BPDEI:DNA and BPDEII:DNA adducts accounted for 14% in the forestomach, 39% in the lung, and 3% in the liver. Another adduct, possibly derived from BP:phenol(s), was detected in lung and liver. Early eluting unidentified DNA-associated radioactivity was also present in each of the tissues and accounted for the majority of the radioactivity (88%) in forestomach, 57% in lung, 97% in liver). Although total DNA-associated radioactivity in liver was approximately 15-fold higher than in lung and 5-fold higher than in forestomach, the specific activities of the BPDEI:adducts and of the BPDEII:adducts were approximately the same in these organs. Addition of alpha-AL or BHA to the diet inhibited BPDEI:DNA adduct formation in the forestomach and liver but not in the lung. The effect of beta-NF was not tissue specific; this aryl hydrocarbon hydroxylase inducer decreased markedly (80 to 90%) BPDEI:DNA adduct formation in all three tissues. The radioactivity associated with the early eluting peaks was also reduced when associated with the early eluting peaks was also reduced when alpha-AL, BHA, or beta-NF was fed to the mice. The inhibition of BPDEI:DNA and BPDEII:DNA adduct formation by alpha-AL, BHA, and beta-NF is discussed in relation to similar studies where these compounds inhibited BP-induced neoplasia.
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology*; D001580:Benzopyrenes / Q000378:metabolism*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004247:DNA / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D019324:beta-Naphthoflavone
D000840:Anisoles; D000970:Antineoplastic Agents; D001571:Benzoflavones; D001580:Benzopyrenes; D005419:Flavonoids; D005663:Furans; C019257:angelica lactone; D002083:Butylated Hydroxyanisole; D019324:beta-Naphthoflavone; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D015107:4-Butyrolactone