Suppression of intestinal polyposis in Apc(Min/+) mice by inhibiting nitric oxide production.
Inducible nitric oxide synthase (iNOS) was shown to be expressed in normal mucosa and adenoma of small and large intestines of Apc(Min/+) mice by reverse transcription-PCR and immunohistochemistry. Administration of the iNOS inhibitor aminoguanidine (1.5 g/liter) in drinking water or an L-arginine-deficient diet to Apc(Min/+) mice resulted in a significant decrease in adenoma development in the small but not the large intestine. Similarly, iNOS-gene knockout Apc(Min/+) mice (Apc(Min/+) iNOS(-/-) or Apc(Min/+) iNOS(-/+)) developed significantly fewer adenomas in both small and large intestines than Apc(Min/+) iNOS(+/+) mice. These results suggest that iNOS-selective inhibitors could be used as a potential chemopreventive agent for colorectal cancers.
Ahn
B
B
Department of Pathology, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, 122-704, Korea.
Ohshima
H
H
D000236:Adenoma / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000172:deficiency; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017491:Genes, APC; D006146:Guanidines / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000201:enzymology; D007414:Intestinal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D007417:Intestinal Polyps / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis
D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C004479:pimagedine