Research of experimental pathology on the model for ulcerative colitis - large bowel cancer

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1) Development of the model for ulcerative colitis - large bowel cancer : Dietary administration of l-hydroxyanthraquinone (HA*) (1%) to rats for approximately 460 days was done. Twenty five rats out of 29 effective animals developed large bowel neoplasms (adenoma or adenocarcinoma). All of these effective rats also developed some pathological changes which are often seen in ulcerative colitis patients. They were crypt abscess, melanosis, erosion or regenerative epithels. These results indicate that HA* induces simultaneously pathological changes resembling those appeared in the case of ulcerative colitis and neoplasms.2) Cell kinetic analysis of proliferative epithelial cells in rats given HA* : Sequential observation of the large bowels of rats exposed to HA* (1%) by sacrifice of animals at 4, 8 or 12 months after the start of tye dietary exposure. Thickness, number of cells constituting crypt, labelling indices of BrdU in the crypt cells, ODC activity and appearance of the changes s … More uch as erosion, crypt abscess of the large bowels of rats with HA* were respectively greater than those of control animals. Each of the biomarkers became greater responding to the exposure-time of HA*.3) Tumor-promotive effect of 1, 8-dihydroxianthraquinone (danthron) in the large of mice : Modifying effect of danthron on dimethylhydrazine (DMH)-induced large bowel carcinogenesis in mice was examined. Incidence of colon neoplasms (adenoma or adenocarcinoma) in mice given DMH together with danthron was significantly higher than that of mice exposed to DMH alone. ODC activity of the large bowel of mice given danthron was much greater than that of controls.Expression of cytokines, TNF-a and IL-la in the large bowel carcinogenesis by MAM acetate and HA* : Expression of the cytokines was examined by RT-PCR method. Expression of the cytokines in the colon neoplasms was stronger than in non-neoplastic mucosa. That of cytokines in the colon mucosa given both agents or either of the agents was aloso greater than in controls. The synergistic effects of HA* with MAM acetate might be related to the biological effects of the cytokines expressed in the inflammatory conditioned generated by HA*. Less