Suppression of azoxymethane-induced colonic aberrant crypt foci by a nitric oxide synthase inhibitor.
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.
Kawamori
T
T
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan. tkawamor@gan2.ncc.go.jp
Takahashi
M
M
Watanabe
K
K
Ohta
T
T
Nakatsugi
S
S
Sugimura
T
T
Wakabayashi
K
K
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D034961:Antigens, Nuclear; D001397:Azoxymethane; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009687:Nuclear Proteins / Q000032:analysis; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D034961:Antigens, Nuclear; D002273:Carcinogens; D009687:Nuclear Proteins; C051963:nucleolar organizer region associated proteins; D019001:Nitric Oxide Synthase; D001397:Azoxymethane; D019331:NG-Nitroarginine Methyl Ester