EFFECT OF BUTYLATED HYDROXYANISOLE, ALPHA-ANGELICA LACTONE, AND BETA-NAPHTHOFLAVONE ON BENZO(ALPHA)PYRENE - DNA ADDUCT FORMATION INVIVO IN THE FORESTOMACH, LUNG, AND LIVER OF MICE

Abstract

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 h after p.o. [per os] 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 and 97% in liver). Although total DNA-associated radioactivity in liver was .apprx. 15-fold higher than in lung and .apprx. 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 (80-90%) BPDEI:DNA adduct formation in all 3 tissues. The radioactivity 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.