Ohuchi 30_5

The present study was designed to investigate the effects of fermented miso (fermented soybean paste) on the induction of colon tumors by azoxymethane (AOM) in male F344 rats. A total of 91 rats, 6 weeks of age, were divided into 5 groups and given weekly subcutaneous injections of AOM (15 mg/kg body wt) for 3 weeks. The animals were placed on diets one week before the first AOM dose: commercial normal control MF diet or a diet containing 10% 2-year, 180-day fermented, or 3-4-day fermented miso. There were no differences in body and organ weights, and no aberrant crypt foci (ACF) among carcinogen-treated groups at week 25. The rates of tumor incidence were 45%, 85%, 75% and 60% with the 2-year, 180-day, and 3-4-day fermented miso and MF, respectively, and those for colon tumors were 34%, 55%, 60% and 55%, respectively. The size of welldifferentiated adenocarcinomas and total (well differentiated and signet ring cell) adenocarcinomas in the 180-day fermented miso group was significantly smaller than that in the 2-year fermented miso and MF+AOM groups. Nuclear staining of ß-catenin in colon tumors was increased for the 34-day fermented miso compared to the 180-day fermented miso. Cdx2 staining tendency was decreased in colon tumors and adenocarcinomas compared to normal mucosa and ACF, which stained in 100% of cases. In addition, the PCNA index was significantly reduced in the 180-day group compared with those groups receiving the 3-4-day fermented miso and MF diet. The germinal region was also decreased. The present results indicate that dietary supplementation with 180-day fermented dietary miso could act as a chemopreventive agent for colon carcinogenesis. Introduction The incidence of breast and prostate cancer in Asian countries with a high consumption of soy and soy-based products is lower than the United States. However, the rates for these cancers have shown an increase in the second generation of families that migrate to America from these countries as their diet becomes westernized (1). Thus, environment (lifestyle) may have a greater influence than genetic background. Miso, a traditional ingredient of the Japanese diet, is fermented from soybeans, rice, wheat or oats, and its major constituents are vitamins, microorganisms, salt, minerals, plant proteins, carbohydrates, and fat. It is used on a daily basis to flavor food in Japan and other parts of Asia, and remains an essential ingredient for Japanese style cooking. We have described chemopreventive effects of miso against intestinal injury in X-irradiated mice (2), and it has also been reported to reduce the occurrence of liver (3,4) and gastric tumors (5), as well as the development of aberrant crypt foci (ACF) in experimental animals in a dose-dependent manner (6). However, the effects of soy beans and related foodstuffs on cancer risk are complex (7). Recently, our experimental studies provided evidence that long-term fermented miso is quite effective in aiding the recovery of stem cells in the small intestinal crypts after irradiation (8), and decreasing the development of azoxymethane (AOM)-induced ACF (9), gastric tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine (10) and pulmonary adenocarcinomas induced by dipropanolnitrosamine (11). To determine whether soy beans alone or fermentation processes have a role, the present study was performed to assess the chemopreventive potential of samples after different periods of fermentation. Materials and methods Animals. Male F344/DuCrj rats, 5 weeks of age at commencement, were purchased from Charles River and housed five to a polycarbonate cage under a constant temperature of 24±2 ̊C and relative humidity of 55±10%, with a 12:12-h light-dark cycle. The animals were maintained according to the Guide for the Care and Use of Laboratory Animals established by Hiroshima University. All were given free access to a ONCOLOGY REPORTS 14: 1559-1564, 2005 Decrease in size of azoxymethane induced colon carcinoma in F344 rats by 180-day fermented miso YOSHIE OHUCHI1, YUKI MYOJIN1, FUMIO SHIMAMOTO1, NAOKI KASHIMOTO2, KENJI KAMIYA2 and HIROMITSU WATANABE2 1Department of Health Science, Hiroshima Prefectural Women's University, 1-1-71 Ujina-higashi, Minami-ku, Hiroshima 734-8558; 2Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan Received May 30, 2005; Accepted July 25, 2005 _________________________________________ Correspondence to: Dr Hiromitsu Watanabe, Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan E-mail: [email protected]