Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats

Cancer Lett. 2000 Aug 31;157(1):15-21. doi: 10.1016/s0304-3835(00)00461-4.

Abstract

The modifying effects of dietary administration of ferulic acid (FA) on azoxymethane (AOM)-induced colon carcinogenesis were examined in three experiments with male 344 rats. In the first experiment, the modifying effect of FA on AOM (15 mg/kg body weight, once a week, for 3 weeks)-induced formation of aberrant crypt foci (ACF) was examined in five groups. Numbers of ACF/colon of groups 2 (AOM+250 ppm FA) and 3 (AOM+500 ppm FA) at the termination (5 weeks after the start) were smaller than of group 1 (AOM alone). Those of ACF/cm(2) of group 3 were also smaller than of group 1 (P<0.05). In the second experiment, a long-term assay for the effects of FA was conducted with seven groups. At the termination (35 weeks), groups 2 and 3 which were given FA during the initiation phase at doses of 250 and 500 ppm, respectively, had lower incidences of colonic carcinomas (23 and 27%, respectively) than group 1 which was given AOM alone (59%; P<0.05). In the third experiment, to determine whether FA could modify the activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR) in liver and colon, 60 rats were gavaged with FA at four doses (0, 25, 50, 100 mg/kg body weight). Dosing of 100 mg/kg significantly elevated GST activity in liver (P<0.03), and QR activities in liver and colonic mucosa (P<0.01 and P<0.02, respectively), suggesting that detoxifying enzymes are related to the blocking effect of FA on AOM-induced colon carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / therapeutic use*
  • Anticarcinogenic Agents / toxicity
  • Azoxymethane / antagonists & inhibitors
  • Carcinogens
  • Colon / drug effects
  • Colon / enzymology
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / prevention & control*
  • Coumaric Acids / therapeutic use*
  • Coumaric Acids / toxicity
  • Diet
  • Glutathione Transferase / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / enzymology
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / prevention & control
  • Rats
  • Rats, Inbred F344

Substances

  • Anticarcinogenic Agents
  • Carcinogens
  • Coumaric Acids
  • ferulic acid
  • NAD(P)H Dehydrogenase (Quinone)
  • Glutathione Transferase
  • Azoxymethane