Inhibition by white tea of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced colonic aberrant crypts in the F344 rat

Nutr Cancer. 2001;41(1-2):98-103. doi: 10.1080/01635581.2001.9680618.

Abstract

There is growing interest in the potential health benefits of tea, including the anticarcinogenic properties. We report here that white tea, the least processed form of tea, is a potent inhibitor of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colonic aberrant crypts in the rat. Male Fischer 344 rats were treated for 8 wk with white tea (2% wt/vol) or drinking water alone, and on alternating days in experimental Weeks 3 and 4 the animals were given PhIP (150 mg/kg body wt p.o.) or vehicle alone. At the end of the study there were 5.65 +/- 0.81 and 1.31 +/- 0.27 (SD) aberrant crypt foci per colon in groups given PhIP and PhIP + white tea, respectively (n = 12, P < 0.05). No changes were detected in N-acetyltransferase or arylsulfotransferase activities compared with controls, but there was marked induction of ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, and UDP-glucuronosyltransferase after treatment with white tea. Western blot revealed corresponding increases in cytochrome P-450 1A1 and 1A2 proteins. Enzyme assays and Western blot also revealed induction of glutathione S-transferase by white tea. There was less parent compound and 4'-hydroxy-PhIP but more PhIP-4'-O-glucuronide and PhIP-4'-O-sulfate in the urine from rats given PhIP + white tea than in urine from animals given carcinogen + drinking water. The results indicate that white tea inhibits PhIP-induced aberrant crypt foci by altering the expression of carcinogen-metabolizing enzymes, such that there is increased ring hydroxylation at the 4' position coupled with enhanced phase 2 conjugation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / administration & dosage
  • Colon / pathology*
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / prevention & control*
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Cytochrome P-450 CYP1A2 / biosynthesis
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Enzyme Induction
  • Glucuronides / urine
  • Glucuronosyltransferase / biosynthesis
  • Glutathione Transferase / biosynthesis
  • Imidazoles / urine
  • Male
  • Oxidoreductases / biosynthesis
  • Precancerous Conditions / prevention & control*
  • Rats
  • Rats, Inbred F344
  • Sulfates / urine
  • Tea*

Substances

  • Anticarcinogenic Agents
  • Glucuronides
  • Imidazoles
  • Sulfates
  • Tea
  • Cytochrome P-450 Enzyme System
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • Oxidoreductases
  • methoxyresorufin-O-demethylase
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2
  • Glucuronosyltransferase
  • Glutathione Transferase