APOPTOSIS, CELL REPLICATION, AND WESTERN-STYLE DIET-INDUCED TUMORIGENESIS IN MOUSE COLON

In this study, feeding Western-style diets (WDs) to mice for a duratio n of two years, without any chemical carcinogen led to the development of gross colonic lesions that were histologically classified as dyspl astic crypts and focal hyperplasias with or without atypical nuclei. T o better understand early biological events contributing to the develo pment of colonic neoplasia, grossly normal colonic mucosa was investig ated; mitotic and apoptotic colonic epithelial cells, atypical mitosis , and atypical nuclei mere studied. A significant and transient increa se of mitotic activity in the basal and intermediate portions of the c olonic crypts was seen in young mice after feeding them the WDs. This was accompanied by diffuse activation of apoptosis of the colonic epit helial cells. In tile middle of the rodents' life span, after administ ration of both the WDs and control diet, tile rodents developed a mark ed depletion of apoptotic epithelial cells in the mid-region of tile c olonic crypts; this mas followed bg the expansion of an epithelial cel l population containing atypical nuclei, and the emergence of the gros s lesions noted above. With this sequence of events, prolonged feeding of WDs to mice produced wingle-crypt dysplastic lesions and focal hyp erplasias indicative of tumorigenesis.