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Suppression of Intestinal Polyposis in Apc^Min/+ Mice by Inhibiting Nitric Oxide Production

Department of Pathology, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, 122-704, Korea [B. A.], and Unit of Endogenous Cancer Risk Factors, International Agency for Research on Cancer, 69372, Lyon, Cedex 08, France [H. O.]

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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