Dietary chemoprevention of PhIP induced carcinogenesis in male Fischer 344 rats with tomato and broccoli

PLoS One. 2013 Nov 27;8(11):e79842. doi: 10.1371/journal.pone.0079842. eCollection 2013.

Abstract

The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli powders. Male Fischer 344 rats (n = 45) were randomized into the following treatment groups: control (AIN93G diet), PhIP (200 ppm in AIN93G diet for the first 20 weeks of the study), or tomato + broccoli + PhIP (mixed in AIN93G diet at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks). Study animals were monitored for 52 weeks and were euthanized as necessary based on a set of criteria for health status and tumor burden. Although there appeared to be some hepatic and intestinal toxicity due to the combination of PhIP and tomato + broccoli, these rodents had improved survival and reduced incidence and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone treated group. Rats eating tomato + broccoli exhibited a marked decrease in the number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in situ (cribiform PIN/CIS) lesions and in the incidence of invasive intestinal adenocarcinomas and skin carcinomas. Although the apparent toxic effects of combined PhIP and tomato + broccoli need additional study, the results of this study support the hypothesis that a diet rich in tomato and broccoli can reduce or prevent dietary carcinogen-induced cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed
  • Animals
  • Body Weight
  • Brassica*
  • Carcinogens / toxicity*
  • Cell Transformation, Neoplastic / chemically induced*
  • Chemoprevention*
  • Dietary Supplements*
  • Disease Models, Animal
  • Glutathione S-Transferase pi / metabolism
  • Imidazoles / toxicity*
  • Immunohistochemistry
  • Lipids / blood
  • Male
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Organ Size
  • Rats
  • Solanum lycopersicum*

Substances

  • Carcinogens
  • Imidazoles
  • Lipids
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • Glutathione S-Transferase pi