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ApcMin/+ 마우스의 소화관 폴립발생에 대한 1,4-PBIT의 암예방 효과 Chemopreventive Effect of 1,4-PBIT, a Selective iNOS Inhibitor, on Intestinal Polyposis of ApcMin/+ Mice

대한암예방학회지 2000년 5권 2호 p.87 ~ 93
안병우, 김대중, 남기택, 강진석, 김기석, 최미나, 박기호, 홍충만, 원도희, 장자준, 장동덕,
소속 상세정보
안병우 ( Ahn Byeong-Woo ) 
식품의약품안전청 국립독성연구원 독성병리과
김대중 ( Kim Dae-Joong ) 
식품의약품안전청 국립독성연구원 독성병리과
남기택 ( Nam Ki-Taek ) 
식품의약품안전청 국립독성연구원 독성병리과
강진석 ( Kang Jin-Seok ) 
식품의약품안전청 국립독성연구원 독성병리과
김기석 ( Kim Ki-Sok ) 
식품의약품안전청 국립독성연구원 독성병리과
최미나 ( Choi Mi-Na ) 
식품의약품안전청 국립독성연구원 독성병리과
박기호 ( Park Ki-Ho ) 
식품의약품안전청 국립독성연구원 독성병리과
홍충만 ( Hong Choong-Man ) 
식품의약품안전청 국립독성연구원 독성병리과
원도희 ( Won Do-Hee ) 
식품의약품안전청 생약평가부
장자준 ( Jang Ja-June ) 
서울대학교 의과대학 병리학교실
장동덕 ( Jang Dong-Deuk ) 
식품의약품안전청 국립독성연구원 독성병리과
KMID : 0603520000050020087   

Abstract


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.

키워드

Apc; iNOS; min mouse; NO; 1;4-PBIT; Polyp

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