Abstract
The effects of α-angelica lactone (α-AL), butylated hydroxyanisole (BHA), and β-naphthoflavone (β-NF) on the amount of benzo(α)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 highpressure 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 (±)-7β,8α-dihydroxy-9α, 10α-epoxy-7,8,9,10-tetrahydrobenzo (α)pyrene (BPDEI):deoxyguanosine adduct. The (±)-7β,8α-dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydrobenzo(α)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, and 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 α-AL or BHA to the diet inhibited BPDEI:DNA adduct formation in the forestomach and liver but not in the lung. The effect of β-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 α-AL, BHA, or β-NF was fed to the mice. The inhibition of BPDEI:DNA and BPDEII:DNA adduct formation by α-AL, BHA, and β-NF is discussed in relation to similar studies where these compounds inhibited BP-induced neoplasia.