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colorectal carcinomas.4. The relationship between the development of the gastrointestinal carcinoma and both the bile acid and the lysozymeGenerally, bile acid has been thought to be devel-opment of the gastrointestinal carcinoma including CRC and the carcinoma of the remnant gastric mucosa, from experimental studies19, 20). We have detected the cellular proliferation including lyso-zyme, which exists in Pa, in the nearby mucosa of the carcinoma of the remnant gastric mucosa21). These findings have pointed out the retionship between the development of that carcinoma and the bile acid.Our tests on the animals have showed that the bile acid enhanced gastric carcinogenesis after oral administration of N-methyl-N’-nitro-N-nitrosoguani-dine, while the lysozyme which is also included in Paneth cell and has been thought to be related to the conversion of bile acid in the small intestine and to defence mechanisms in the gastrointestinal tract, suppressed the effect of bile acid on the development of gastric carcinoma in the rat22) (Figure 4).ConsiderationThese findings described above reveal the consideration described below.Although CR-PaM is gene-unstable mucosa, some CR-PaM may be the pre-neoplastic condition and most of that is the mucosa with no relationship Figure 4　The relationship between the development of the gastric carcinoma and both the bile acid and the lysozymeThe bile acid enhanced gastric carcinogenesis after oral administration of N- methyl-N’-nitro-N-nitrosoguanidine (MNNG), while the lysozyme suppressed the effect of bile acid on the development of gastric carcinoma in the rat.to the development of the CEN, because CEN existed whole large bowel when CR-PaM was detected in the proximal colon. One of the reasons of the appearnce of Pa in the colorectal mucosa is anti-overflow of the bile acid (the bile juce) in the large bowel, because the lysozyme which is also in Pa restrained the bile acid’s promotor effect of the gastrointestinal carcinoma. Thus, the lifestyle of European and American related with the increase of the incidence of CRA-Pa is thought to be based on the over-inflow of bile juce in the large bowel, and is inevitably concluded to the continous intake of high-fat foods. The relationship between the development of the colorectal carcinona and the continous intake of high-fat foods has been pointed out from the epide-miological examinations and the tests on the animals23, 24). However, this phenomenon described above has been unclear on the researches for the human cells or organs. Pathological examinations have showed many histogenesis of the CRC, for example, the adenoma-carcinoma sequence described above, de-novo development, serrated lesions, etc.. At least, the increase of the CRC in Japanese, is thought to be related with the continous intake of high-fat foods and the adenoma-carcinoma sequence.Recent studies have showed that Pa constitute the niche for stem cells in intestinal crypts25, 26). Thus, CRA-Pa may be called CRA with niche condition and the existence of CRA-Pa is thought to be more important in the development of CRC.425