Effect of alpha-naphthyl isothiocyanate on 2-amino-3-methylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in rats.

The modifying effects of alpha-naphthyl isothiocyanate (ANIT) on 2-amino-3-methylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis were investigated in female Sprague-Dawley (SD) rats, and the hepatic activities of the phase II detoxifying enzymes glutathione S-transferase (GST) and quinone reductase (QR) were also assayed. Ninety-eight rats were divided into 4 groups. Starting at 6 weeks of age, rats were fed the high-fat diet without ANIT (Groups 1 and 4) or the experimental diet (high-fat diet mixed with 400 ppm ANIT, Groups 2 and 3). At 7 weeks of age, Groups 1 and 2 were given PhIP in corn oil (85 mg/kg body weight, 8 times for 11 days) by intragastric intubation. One week after the last PhIP injection, 5 rats in each group were sacrificed to assay GST and QR activities, and the experimental diets for Groups 2 and 3 were switched to the high-fat diet without ANIT until termination of the experiment. Group 4 served as the vehicle control. All rats were sacrificed at 24 weeks after the start of the experiment. At termination of the experiment, mammary tumours were detected in Groups 1 (PhIP alone) and 2 (PhIP + ANIT) and were shown histologically to be adenocarcinomas; their incidences (multiplicities) were 56.3% (1.66 +/- 2.31/rat) in Group 1 and 6.7% (0.07 +/- 0.25/rat) in Group 2 (p < 0.001). Mean sizes of the tumours were 10.6 +/- 5.3 mm in Group 1 and 6.5 mm in Group 2. No mammary tumours were observed in rats of Groups 3 and 4. In addition, ANIT treatment significantly increased the activities of GST and QR in the livers of rats in Groups 2 and 3 as compared to Groups 1 and 4. These results imply that the isothiocyanate compound ANIT shows potent inhibitory effects on mammary carcinogenesis induced by PhIP in female SD rats when administered during the initiation stage.