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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anticarcinogenic Agents / administration & dosage
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Anticarcinogenic Agents / pharmacology*
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Anticarcinogenic Agents / therapeutic use
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Antigens, Nuclear
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Azoxymethane
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Body Weight / drug effects
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Carcinogens
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Cell Division / drug effects
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Cell Nucleus / chemistry
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Cell Nucleus / drug effects
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Cell Nucleus / pathology
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Colon / drug effects
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Colon / pathology
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Colonic Neoplasms / chemically induced
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Colonic Neoplasms / enzymology
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Colonic Neoplasms / pathology
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Colonic Neoplasms / prevention & control*
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Intestinal Mucosa / drug effects
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Intestinal Mucosa / pathology
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Male
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NG-Nitroarginine Methyl Ester / administration & dosage
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NG-Nitroarginine Methyl Ester / adverse effects
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NG-Nitroarginine Methyl Ester / pharmacology*
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NG-Nitroarginine Methyl Ester / therapeutic use
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nuclear Proteins / analysis
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Precancerous Conditions / chemically induced
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Precancerous Conditions / drug therapy
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Precancerous Conditions / enzymology
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Precancerous Conditions / pathology
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Precancerous Conditions / prevention & control*
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Rats
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Rats, Inbred F344
Substances
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Anticarcinogenic Agents
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Antigens, Nuclear
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Carcinogens
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Nuclear Proteins
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nucleolar organizer region associated proteins
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Nitric Oxide Synthase
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Azoxymethane
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NG-Nitroarginine Methyl Ester