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Effect of Butylated Hydroxyanisole, -Angelica Lactone, and ß-Naphthoflavone on Benzo()pyrene:DNA Adduct Formation in Vivo in the Forestomach, Lung, and Liver of Mice

Laboratory of Pharmacology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709

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

¹ Present address: Toxicology Research and Testing Program, National Institute of Environmental Health Sciences, Research Triangle Park, N. C. 27709.

² Present address: Metabolism Section, Environmental Health Laboratory, Department of Medicine and Environmental Health, Monsanto Company, St. Louls, Mo. 63110.

³ To whom requests for reprints should be addressed.

Received 6/ 5/81. Accepted 12/15/81.