Dietary cholesterol enhances preneoplastic aberrant crypt formation and alters cell proliferation in the murine colon treated with azoxymethane.
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.
Kendall
C W
CW
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada.
Janezic
S A
SA
Friday
D
D
Rao
A V
AV
D000704:Analysis of Variance; D000818:Animals; D001397:Azoxymethane; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004198:Disease Susceptibility; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D011897:Random Allocation
D002791:Cholesterol, Dietary; D001397:Azoxymethane