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KMID : 0603520000050020087
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Journal of Korean Association of Cancer Prevention
2000 Volume.5 No. 2 p.87 ~ p.93
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Chemopreventive Effect of 1,4-PBIT, a Selective iNOS Inhibitor, on Intestinal Polyposis of ApcMin/+ Mice
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Ahn Byeong-Woo
Kim Dae-Joong
Nam Ki-Taek
Kang Jin-Seok
Kim Ki-Sok
Choi Mi-Na
Park Ki-Ho
Hong Choong-Man
Won Do-Hee
Jang Ja-June
Jang Dong-Deuk
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Abstract
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Accumulating evidences indicate that over production of nitric oxide (NO) is involved in the pathogenesis of colorectal cancer in both rodents and humans. Inducible nitric oxide synthase (iNOS) is responsible for the over production of NO in a variety of parenchymal cells and macrophages. Min (multiple intestinal neoplasia) mice, which have germ-line nonsense mutation at codon 850 of Apc gene, spontaneously develop multiple adenomas in small and large intestines at the age of 10∼12 weeks. In the present study we utilized ApcMin/+Min/+ mice to investigate the role of iNOS on the intestinal adenoma development. We have found that iNOS protein are expressed in normal mucosa of small and large intestines of most Min mice. In order to suppress iNOS we administered S,S´-1,4-phenylene bis(1,2-ethanediyl)bis-isothiourea (dihydrobromide) (PBIT), a selective iNOS inhibitor in diet (50 ppm). The number of adenomas in small intestines significantly decreased in ApcMin/+Min/+mice receiving PBIT in diet. The tumor incidence and multiplicity in colorectal tissues also significantly decreased in PBIT-given mice, comparing with those receiving control diet. Immunohistochemical expression of iNOS was decreased in intestinal tissues from PBIT-given mice, comparing with those from control mice. These results suggest that NO produced by iNOS plays an important role as an endogenous factor in the development of intestinal polyposis in mice and PBIT, a selective iNOS inhibitor, may act as a potential chemopreventive agent for colorectal cancers.
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KEYWORD
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Apc, iNOS, min mouse, NO, 1, 4-PBIT, Polyp
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