Prostate Mutations in Rats Induced by the Suspected Human Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Male lacI transgenic rats were fed a diet containing 200 ppm of 2-amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine (PhIP), a heterocyclic amine present in cooked meats. PhIP was found to be a powerful prostate mutagen. After 61 days of treatment, the lacI mutant frequency was 71 × 10 −5 , >20-fold higher than the spontaneous mutant frequency of 3.2 × 10 −5 . The predominant PhIP-induced mutations were G:C→T:A transversions and deletions of G:C bp. The results directly link PhIP-induced mutations with the earlier observation of PhIP-induced prostate cancer in rats and suggest that exposure to dietary PhIP could be a risk factor in the incidence of human prostate cancer.