Suppression of azoxymethane-induced colonic aberrant crypt foci by a nitric oxide synthase inhibitor

Cancer Lett. 2000 Jan 1;148(1):33-7. doi: 10.1016/s0304-3835(99)00310-9.

Abstract

Nitric oxide synthase (NOS), an important bioregulator of a variety of biological processes, is overexpressed in colonic tumors of humans and rodents. In this study, effects of L-N(G)-nitroarginine methyl ester (L-NAME), a NOS inhibitor, on development of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in F344 male rats were investigated. Six-week-old male F344 rats were fed diets containing 0 or 100 ppm L-NAME, and given s.c. injections of AOM at 15 mg/kg body wt, once a week for 2 weeks. At 17 weeks of age, all animals were sacrificed and their colons were evaluated for numbers of ACF. Feeding of 100 ppm L-NAME inhibited the development of ACF in different sizes by 24-39%, those containing four or more crypts being most markedly affected. Assessment of silver-stained nucleolar organizer regions protein (AgNORs)/nucleus further revealed a 44% reduction by administration of L-NAME. These results suggest that the NOS inhibitor, L-NAME, may be an effective chemopreventive agent against colon carcinogenesis due to depression of cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / pharmacology*
  • Anticarcinogenic Agents / therapeutic use
  • Antigens, Nuclear
  • Azoxymethane
  • Body Weight / drug effects
  • Carcinogens
  • Cell Division / drug effects
  • Cell Nucleus / chemistry
  • Cell Nucleus / drug effects
  • Cell Nucleus / pathology
  • Colon / drug effects
  • Colon / pathology
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Male
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • NG-Nitroarginine Methyl Ester / adverse effects
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • NG-Nitroarginine Methyl Ester / therapeutic use
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nuclear Proteins / analysis
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / drug therapy
  • Precancerous Conditions / enzymology
  • Precancerous Conditions / pathology
  • Precancerous Conditions / prevention & control*
  • Rats
  • Rats, Inbred F344

Substances

  • Anticarcinogenic Agents
  • Antigens, Nuclear
  • Carcinogens
  • Nuclear Proteins
  • nucleolar organizer region associated proteins
  • Nitric Oxide Synthase
  • Azoxymethane
  • NG-Nitroarginine Methyl Ester