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-alpha-difluoromethylomithine (DFMO), beta-naphthoflavone (beta-NF), alph a-naphthoflavone (alpha-NF), indole-3-carbinol (I3C) and protocatechuic aci d (PCA) on alpha-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induc ed 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 I: DAD, 200 p pm; aspirin, 400 ppm; DFMO, 400 ppm; beta-NF, 1000 ppm; Experiment 2: alpha -NF, 1000 ppm; I3C, 1000 ppm; PCA, 2000 ppm) for an initial 4 weeks. The ex periments were terminated after 25 weeks. In Experiment I, exposure of beta -NF decreased the incidence and multiplicity of total mammary tumors (fibro adenoma, intraductal carcinoma and invasive ductal carcinoma) (P < 0.001 an d P < 0.0001), and lowered the incidence of ductal carcinoma (P < 0.0001). DAD lowered the incidence of ductal carcinoma and decreased the multiplicit y of the total tumors (P < 0.01 and P < 0.005). Furthermore, aspirin decrea sed the total tumors (P < 0.05). In Experiment 2, alpha-NE decreased the mu ltiplicity of ductal carcinoma (P < 0.05). These results suggest that alpha -NF, beta-NF, DAD or aspirin could be chemopreventing agents for mammary ne oplasia. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.