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 biol ogical processes, is overexpressed in colonic tumors of humans and rodents. In this study, effects of L-NG-nitroarginine methyl ester (L-NAME), a NOS inhibitor, on development of aberrant crypt foci (ACF) induced by azoxymeth ane (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 si zes by 24-39%, those containing four or more crypts being most markedly aff ected, Assessment of silver-stained nucleolar organizer regions protein (Ag NORs)/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 cel l proliferation. (C) 2000 Elsevier Science ireland Ltd. All rights reserved .