Dietary cholesterol enhances the induction and development of colonic preneoplastic lesions in C57BL/6J and BALB/cJ mice treated with azoxymethane.
The effect of dietary cholesterol on the induction and development of colonic precursor lesions was determined in two mouse strains, C57BL/6J and BALB/cJ, which differ in their metabolism of cholesterol. Mice were randomized into four groups and fed a cholesterol-free or a 1.25% cholesterol diet during and/or subsequent to four weekly injections of azoxymethane (5 mg/kg body wt.). Dietary cholesterol significantly increased the number of aberrant crypt foci (P less than 0.0001), enhanced cell proliferation (P less than 0.0001) and induced alterations in the proliferative pattern and crypt morphometrics in the colonic epithelium of both mouse strains. While C57BL/6J mice developed a greater number of aberrant crypt foci than BALB/cJ mice (p less than 0.0001), a significant diet-strain interaction effect was not observed. The present results indicate that dietary cholesterol enhances the induction and development of chemically-induced colonic precancerous lesions but this process is not affected by genetic differences in cholesterol metabolism, as represented by the two strains of mice studied.
Rao
A V
AV
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada.
Janezic
S A
SA
Friday
D
D
Kendall
C W
CW
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D002455:Cell Division; D002791:Cholesterol, Dietary / Q000633:toxicity*; D003043:Cocarcinogenesis; D015179:Colorectal Neoplasms / Q000209:etiology*; D005260:Female; D007422:Intestines / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011230:Precancerous Conditions / Q000209:etiology*
D002791:Cholesterol, Dietary; D001397:Azoxymethane