Key words: superoxide dismutase, colo-rectal cancer, immunohistochemistry

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1 Key words: superoxide dismutase, colo-rectal cancer, immunohistochemistry

2 Table I Immunohistochemical stainins of SOD in the colorectal cancer Histological diagnosis normal mucosa # cancer well diff. moderate diff. muclnous -, not stained. t, weakly or partly stained. *f, stronhly stained. #, adjacent normal mucosa to each cancer Fig. 1 Immunohistochemical staining of Cu/Zn SOD in the normal mucosa of colon ( x 80). Cu/Zn SOD was stained weakly in the normal mucosa of colon, and localized predominantly in the basal part of them. Fig. 3 Immunohistochemical staining of Mn SOD in the colon cancer ( x 40). Mn SOD nas stained in all colo-rectal cancers, and was stained granularly in the cytoplasm.

3 Table 2 The concentration of SOD in the tissue of colorectal cancer Histological diagnosis Cu/Zn SOD (ngl-g normal mucosa # well diff. ca. moderate dif{. ca.

4 8) Kurobe N, Suzuki F, Okajima K et al: Sensitive enzyme immunoassay for human Cu/Zn superoxide dismutase. Clin Chim Acta 187 : 11-20, ) Sternberger LA, Hardy PH, Cuculis JJ et al : The unlabeled antibody enzyme method of im- munochemistry, preparation and properties of soluble antigen antibody complex (horseradish peroxidase) and its use in identification. J Histochem Cytochem 18: , 1970 l0) Kato K, Asai R, Shimizu A et al: Immunoassa1, of three enolase isozymes in human serum and in blood cells. Clin Chim Acta 127 : , r983 11) Kato K, Hamaguchi Y, Okawa S et al : Use of rabbit IgG-loaded silicone piece for the sandu'ich enzyme immunoassay for macromolecular antigens. J Biochem 8l : , ) Layne E: Spectrophotometric and turibidmetric methods for measuring proteins. Methods Enzymol 3' , ) Bradford MM : A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: , ) Sykes JA, McCormack FX Jr, O'Brien TJ: A preliminary study of the superoxide dismutase content of some human tumors. Cancer 38 j , t978 15) Marklund SL, Westman NG, Lundgren E et al: Copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dis- mutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues. Cancer Res 42: lgbb- 1961, ) Loven DP, Oberley LW, Rousseau FM et al : Superoxide dismutase activity in I,Zdimethylhydrazinbe-induced rat colon adenocarcinoma. J Natl Cancer Inst 65:3TT- 381, ) Hoffman CEJ, Webster NR, Wiggins PA et al: Free radical detoxifying systems in human colorectal cancer. Br J Cancer 51i.1ZT ) Sinha BK, Mimnaugh EG, Rajagopalan S et al : Adriamycin activation and oxygen free radical formation in human breast tumor cells; protective role of glutathione peroxidase in adriamycin resistance. Cancer Res 49: , ) Baker SJ, Fearon ER, Vogelstein B et al:

5 1ee7+.7 E Chromosome 17 deletion and p53 gene mutation in colorectal carcinoma. Science 244: , ) Tahara E: Growth factors and oncogenes in human gastrointestinal carcinomas. J Cancer Res Clin Oncol 116 : , ) Yasui W, Sumiyoshi H, llata J et al : Expres, sion of epidermal growth factor receptor in human gastric and colonic carcinoma. Cancer Res 41 : , 79BB 22) Derynck R, Goeddel DV, Ullich A et al : Synthesis of messenger RNAs for transforming growth factors a and B and the epidermal growth factor receptor by human tumors. Can_ cer Res 47 : , I1BT 23) Shweiki D, Itin A, Soffer D et al : Vascular endothelial growth factor induced by hypoxia may mediate hypoxiainitiated angiogerresis. Superoxide Dismutase in the Colo-rectal Cancer Katsumi Iwase, Toru Tsujimura, Tsunekazu Hanai, Shin Jimbo and Kaoru Miura Department of Surgery, Fujita Ilealth University School of Medicine The localizations of Cu/Zn and Mn superoxide dismutase (SOD), which catalyzes the dismutation of superoxide radicals (Or) to O, and HrOr, were studiecl in 26 colo-rectal carcinomas by an immunohistochemical technique. We employed l0'% formalin fixed paraffin embedded thin sections and used antihuman Cu/Zn' and Mn-SoD antibodies. The concentrations of both SoDs in these tissues were also measured by a sandwich enzyme imrnunoassay technique- Both Cu/Zn and Mn SOD were more clearly immunohistochemically stained in cancer cells than in the normal mucosal layer of the large intestine. Among cancer tissues, both stained more clearly in many well-differentiated carcinomas. The concentration of Mn SOD was significantly elevated in cancer tissues, especially in well-differentiated malignancies. The ratio of the tissue concentration of Mn SoD to that of cu/zn SoD was also high in the well-differentiated carcinomas. Cu/Zn SOD changed its intra-cellular localization from a predominance in the basal portions of normal mucosal cells to a homogeneous distribution in the cytoplasm of cancer cells' In conclusion, both SODs appear to be related to tumor growth, and Mn SOD may play a role in the differentiation of colo-rectal carcinoma. Reprint requests: Katsumi Iwase Department of Surgery, Fujita Health University School of Medicine Kutsukake, Toyoake, JAPAN

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