Dietary cholesterol enhances preneoplastic aberrant crypt formation and alters cell proliferation in the murine colon treated with azoxymethane

Abstract

The effect of dietary cholesterol on the development of colonic preneoplastic aberrant crypts, as well as its influence on the proliferative status of the intestinal epithelium, was investigated in mice exposed to the chemical carcinogen azoxymethane. Two strains of mice, C57BL/6J and BALB/cJ, were fed a semisynthetic diet containing 0% (control), 1.25%, or 5.00% cholesterol for eight weeks. During the first four weeks of the experiment, mice were given weekly injections of azoxymethane. Cholesterol supplementation significantly increased the formation of aberrant crypts (p less than 0.0001), enhanced the rate of cell proliferation (p less than 0.0001), altered the cell proliferative pattern, and increased crypt height (p less than 0.05) and the total number of cells per crypt (p less than 0.01) in the colonic epithelium of both mouse strains. C57BL/6J mice developed a greater number of aberrant crypts (p less than 0.0001). However, a diet-strain interaction was not observed. The results of this study indicate that dietary cholesterol enhances colon carcinogenesis in the murine colon and therefore may be an important factor in the etiology of large bowel cancer in humans.

Comparative Effect of Dietary Olive, Safflower, and Linseed Oils on Spontaneous Liver Tumorigenesis in C3H/He Mice.

“…But studies on the correlation between dietary fats and the generation of spontaneous tumor are limited. Dietary cholesterol enhanced carcinogenesis in the colon of the mice exposed to the chemical carcinogen (13), and even in the mice given no carcinogen, a high level of dietary cholesterol (CHOL) raised risk for the de velopment of large bowel cancer through an increased lumenal concentration of neutral steroid (14). The in crease in plasma CHOL level with aging, which has pre viously been reported (15,16), may link to tumorigene sis during a long time of breeding.…”

Plant stanols induce intestinal tumor formation by up-regulating Wnt and EGFR signaling in ApcMin mice

“…Plant stanol feeding resulted in sixfold higher cholesterol level in the caecum content and our data show that there was a positive correlation between feacal cholesterol level and adenoma number. The elevated level of intraluminal cholesterol is associated with increased carcinogenesis in vivo [2,3]. In our study, enhanced adenoma formation was accompanied by the activation of the Wnt/β-catenin and EGFR signaling, two major pathways in colon carcinogenesis, and these changes were detectable already in the normal appearing mucosa.…”

“…The elevated level of cholesterol derivatives in the colon may lead to a modified gut environment. High intraluminal cholesterol concentration, from dietary and/or endogenous origin, has been associated with enhanced cell proliferation, aberrant crypt formation and tumor formation in the murine colon [2,3].…”

Plant sterols induce intestinal tumor formation in gender-related manner in ApcMin mice

“…Plant sterols reduce cholesterol absorption, and therefore plant sterol enriched functional foods are designed to lower blood cholesterol level. Reduction of cholesterol absorption increases the level of intraluminal cholesterol, and high intraluminal cholesterol concentration has been associated with enhanced cell proliferation, aberrant crypt formation and tumor formation [1,2]. The aim of this study was to investigate, how plant sterols affect intestinal tumorigenesis, sterol composition of the faeces and the intestinal mucosa, and cell signaling in tumor-prone Apc Min mice.…”