INHIBITION INVIVO OF THE FORMATION OF ADDUCTS BETWEEN METABOLITES OF BENZO(A)PYRENE AND DNA BY BUTYLATED HYDROXYANISOLE

Abstract

Antioxidants inhibit the carcinogenic effects of a variety of chemical carcinogens. The effects of butylated hydroxyanisole (BHA) on benzo(a)pyrene(BP)-induced neoplasia and on the formation of BP metabolite:DNA adducts was studied. Following p.o. [oral] administration of a carcinogenic dose of [3H]BP to A/HeJ mice, radioactivity was detected in the DNA of lung and liver. The major adduct in both tissues cochromatographed with the (.+-.)-77b,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 (BPDE11):deoxyguanosine adduct was 10-15% of the BPDE1 adduct in both lung and liver. Another adduct, possibly derived from BP phenol(s), was detected in lung and was 10-20% of the BPDEI adduct. Treatment of animals with BHA decreased in the lung and the liver .apprx. 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. 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.