Inhibition in vivo of the formation of adducts between metabolites of benzo(a)pyrene and DNA by butylated hydroxyanisole.
Antioxidants have been shown to inhibit the carcinogenic effects of a variety of chemical carcinogens. For example, the phenolic antioxidant butylated hydroxyanisole (BHA) has been shown to be a potent inhibitor of benzo(a)pyrene (BP)-induced neoplasia in mouse lung and forestomach. The objective of the present study was to determine whether or nt BHA, under conditions known to result in inhibition of BP-induced neoplasia, affects the formation of BP metabolite:DNA adducts. Following p.o. administration of a carcinogenic dose of [3H]BP to A/HeJ mice, radioactivity was detected in the DNA of both lung and liver. Analysis of the deoxyribonucleosides by high-pressure liquid chromatography showed that the major adduct in both tissues cochromatographed with the (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEI):deoxyguanosine adduct. The 7 beta, 8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEII):deoxyguanosine adduct was 10 to 15% of the BPDEI adduct in both lung and liver. Another adduct, possibly derived from BP phenol(s), was also detected in lung and was 10 to 20% of the BPDEI adduct. Treatment of animals with BHA decreased the amount of the BPDEI adduct in the lung and the liver approximately 55 and 75%, respectively. The decrease in the amount of this adduct in the lung appears to correlate with the inhibition of pulmonary adenoma formation (L. W. Wattenberg, J. Natl. Cancer Inst., 50: 1541-1544, 1973; J. L. Speier, L. K. Lam, and L. W. Wattenberg, J. Natl. Cancer Inst., 60: 605-609, 1978). Thus, BHA appears to inhibit BP-induced pulmonary adenoma formation by inhibiting the amount of the BPDE:DNA adducts formed in lung. Possible mechanisms by which BHA treatment inhibits the formation of BPDE:DNA adducts are discussed.
D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D002083:Butylated Hydroxyanisole / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D004032:Diet; D005260:Female; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism
D000840:Anisoles; D000975:Antioxidants; D001580:Benzopyrenes; D002083:Butylated Hydroxyanisole; D001564:Benzo(a)pyrene; D004247:DNA