Effects of arctiin on PhIP-induced mammary, colon and pancreatic carcinogenesis in female Sprague-Dawley rats and MeIQx-induced hepatocarcinogenesis in male F344 rats

Chemopreventive effects of arctiin, a lignan isolated from Arctium lappa (b urdock) seeds, on the initiation or post initiation period of 2-amino-1-met hyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced mammary carcinogenesis in female rats and on 2-amino-3,8-dimethylimidazo[4,5lf]quinoxaline (MeIQx)-a ssociated hepatocarcinogenesis in male rats were examined. In experiment 1, female Sprague-Dawley (SD) rats were given intragastric doses of 100 mg/kg body wt of PhIP once a week for 8 weeks as initiation. Groups of 20 rats e ach were treated with 0.2 or 0.02% arctiin during or after PhIP initiation. Control rats were fed 0.2 or 0.02% arctiin, or basal diet alone during the experimental period. Animals were killed at the end of week 48. Although t he incidence of mammary carcinomas did not significantly differ among the P hIP-treated groups, multiplicity was significantly decreased in rats given 0.2 (0.7 +/- 0.7, P < 0.05) or 0.02% (1.0 +/- 1.1, P < 0.05) arctiin after PhIP initiation as compared with the PhIP alone controls (2.1 +/- 2.5). The average number of colon aberrant crypt foci was also significantly decreas ed in these two groups. Pancreas acidophilic foci were induced in PhIP trea ted animals with slight decrease in the multiplicity with arctiin during th e initiation phase. For liver carcinogenesis, groups of 15 male F344 rats w ere given a single intraperitoneal injection of diethylnitrosamine (DEN) an d starting 2 weeks later, they were: administered 0.03% MeIQx in the diet, MeIQx together with 0.5% arctiin, 0.1% arctiin or basal diet for 6 weeks. T hey were subjected to two-third partial hepatectomy 3 weeks after DEN initi ation and killed at the end of week 8 for glutathione S-transferase placent al form (GST-P) immunohistochemistry. The numbers and areas of preneoplasti c GST-P positive foci were elevated by the treatment with MeIQx, and furthe r increased by the simultaneous treatment with arctiin. These results indic ate that arctiin has a protective effect on PhIP-induced carcinogenesis par ticularly in the mammary gland in the promotion period. On the other hand, it may have a weak co-carcinogenic influence on MeIQx-induced hepatocarcino genesis. In addition, the results suggested that PhIP is a weak pancreatic carcinogen in female SD rats, targeting acinar cells. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.