Chemoprevention of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine-induced mammary carcinogenesis in rats

Modifying effects of dietary exposure of diallyl disulfide (DAD), aspirin, DL-α-difluoromethylornithine (DFMO), β-naphthoflavone (β-NF), α-naphthoflavone (α-NF), indole-3-carbinol (I3C) and protocatechuic acid (PCA) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis were examined in two experiments with female rats. For both experiments, PhIP in corn oil at a concentration of 85 mg/kg was given to animals via an intragastric tube for eight doses for an initial 4 weeks, and test chemicals were given in the diet (Experiment 1: DAD, 200 ppm; aspirin, 400 ppm; DFMO, 400 ppm; β-NF, 1000 ppm; Experiment 2: α-NF, 1000 ppm; I3C, 1000 ppm; PCA, 2000 ppm) for an initial 4 weeks. The experiments were terminated after 25 weeks. In Experiment 1, exposure of β-NF decreased the incidence and multiplicity of total mammary tumors (fibroadenoma, intraductal carcinoma and invasive ductal carcinoma) (P<0.001and P<0.0001), and lowered the incidence of ductal carcinoma (P<0.0001). DAD lowered the incidence of ductal carcinoma and decreased the multiplicity of the total tumors (P<0.01 and P<0.005). Furthermore, aspirin decreased the total tumors (P<0.05). In Experiment 2, α-NF decreased the multiplicity of ductal carcinoma (P<0.05). These results suggest that α-NF, β-NF, DAD or aspirin could be chemopreventing agents for mammary neoplasia.