Chemoprotection against the formation of colon DNA adducts from the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the rat

Mutat Res. 1997 May 12;376(1-2):115-22. doi: 10.1016/s0027-5107(97)00033-x.

Abstract

The mutagenic heterocyclic aromatic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), is a pyrolysis product in cooked foods that has been shown to be a rat colon carcinogen and has been implicated in the etiology of human colon cancer. In order to identify chemoprotection strategies that could be carried out in humans, a pilot study was conducted in which PhIP-DNA-adduct levels were quantified in the colons of male F344 rats that had been subjected to 16 different putative chemoprotection regimens, followed by a gavage of PhIP (50 mg/kg) and sacrifice 24 h later. The 16 treatments (Oltipraz, benzylisothiocyanate, diallyl sulfide, garlic powder, ethoxyquin, butylated hydroxyanisole, glutathione, indole-3-carbinol, alpha-angelicalactone, kahweol/cafestol palmitates, quercetin, green tea, black tea, tannic acid, amylase-resistant starch, and physical exercise) comprised sulfur-containing compounds, antioxidants, flavonoids, diterpenes, polyphenols, high dietary fiber, etc. The strongest inhibition of PhIP-DNA adduct formation in the colon was observed upon pretreatment with black tea, benzylisothiocyanate, and a mixture (1:1) of kahweol:cafestol palmitates, which resulted in 67, 66, and 54% decreases in colon PhIP-DNA adduct levels, as compared with controls. Preliminary studies on their mechanism of action indicated that only kahweol:cafestol caused a substantial induction of glutathione S-transferase isozymes (GSTs) that are thought to be important in the detoxification of PhIP. Notably, this induction occurred in the liver rather than in the colon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Antimutagenic Agents / pharmacology*
  • Colon / metabolism
  • DNA Adducts / antagonists & inhibitors*
  • Diet
  • Glutathione Transferase / metabolism
  • Imidazoles / antagonists & inhibitors*
  • Male
  • Rats
  • Rats, Inbred F344

Substances

  • Anticarcinogenic Agents
  • Antimutagenic Agents
  • DNA Adducts
  • Imidazoles
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • Glutathione Transferase