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Cancer Res. 2001 Dec 1;61(23):8357-60.

Suppression of intestinal polyposis in Apc(Min/+) mice by inhibiting nitric oxide production.

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Department of Pathology, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, 122-704, Korea.


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.

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