Abstract

The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in well-cooked meats, has been implicated by epidemiology and rodent studies for causing breast, prostate, and colo-rectal cancers. Our aim was to determine if PhIP-induced carcinogenesis can be prevented with tomato + broccoli. 50 male Fisher 344 rats were randomized into 1 of 3 treatment groups, control, PhIP (200 ppm in diet for 20 wks), or PhIP + tomato + broccoli (mixed in AIN93G diet at 10% each and fed with PhIP for 20 wks, and then without PhIP for 32 wks.) During the study rats were euthanized based on health and tumor burden and at 52 wks remaining rats were euthanized and tissues collected for histological analysis. PhIP resulted in reduced body weight, food intake, and weight of the ventral prostate. In rats eating tomato + broccoli the rate of prostatic tumor lesions (cribriform PIN/Carcinoma in situ), invasive intestinal adenocarcinomas and skin tumors (basaloid/squamous/sebaceous) decreased. In the tomato + broccoli + PhIP group there was increased liver and spleen weight accompanied by mononuclear cell infiltrate. Prostatic lesions showed less staining for GSTP1 protein, which is encoded by a gene that is methylated and silenced in ~90% of human prostate cancers. In this model, rodents on a tomato + broccoli diet had improved survival and reduced severity and incidence of PhIP-induced neoplastic lesions.

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