Effects of cacao liquor proanthocyanidins on PhIP-induced mutagenesis in vitro, and in vivo mammary and pancreatic tumorigenesis in female Sprague–Dawley rats

The effects of cacao liquor proanthocyanidins (CLPr) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mutagenesis in vitro and on in vivo carcinogenesis in female Sprague–Dawley (SD) rats were investigated. In the Ames assay using Salmonella typhimurium TA98, CLPr showed strong antimutagenic effects against PhIP when assayed in the presence of S-9 mixture. For determination of the influence on initiation and subsequent development of lesions, CLPr (0.025% or 0.25%) were fed during the period of PhIP application (100 mg/kg given to rats via gastric tubes eight times over 4 weeks), or thereafter until the termination at 48 weeks. CLPr treatments did not affect body or organ weights. The incidences, multiplicities and volumes of mammary tumors in the 0.25% CLPr (post-initiation) group showed a tendency to decrease as compared to PhIP alone group values, although without statistical significance. The incidences of preneoplastic eosinophilic foci in the exocrine pancreas were significantly (P<0.05) decreased in a dose-dependent manner when CLPr were given during the initiation period. These results indicate that CLPr inhibit in vitro mutagenicity of PhIP, as well as rat pancreatic carcinogenesis in the initiation stage, but not mammary carcinogenesis induced by PhIP.