Effect of dietary cellulose on cell proliferation and progression of 1,2-dimethylhydrazine-induced colon carcinogenesis in rats.
The effects of different levels of dietary cellulose on colonic crypt mitotic activity and colon carcinogenesis were studied in 190 male Sprague-Dawley rats. Rats were divided into groups and fed a basal fiber-free diet supplemented with either 0, 5, or 15% pure cellulose (w/w), for periods of 10 weeks (initiation stage) or 32 weeks (promotional stage). Half of the rats in each group were given weekly s.c. injections of 9.5 mg 1,2-dimethylhydrazine (the base) (DMH) for 8 weeks. Some of the rats were killed at 10 weeks while most were killed 22 weeks later. In some groups the dietary cellulose level was changed to a different level at 10 weeks. Food intake and body weight data showed that the rats within each experiment were isocalorically fed. There was a direct correlation between crypt height and the percentage of cellulose in the diet. Addition of 5 or 15% dietary cellulose during the initiation stage of carcinogenesis resulted in a significant increase in crypt height. Increasing dietary cellulose after the initiation stage (0 to 5% and 5 to 15%) or maintaining a high dietary cellulose level throughout both the initiation and promotional stages (15%) resulted in a significant increase in crypt height. A DMH-induced increase in mitotic activity that was observed during the initiation stage was no longer evident after the 22-week promotional stage. The significant DMH-induced increases in proliferative zone height and crypt height that were initially observed during the initiation stage were also observed after the 22-week promotional stage. These data indicate that the initial DMH-induced increases observed in proliferative zone height and crypt height are irreversible. Addition of 5 or 15% cellulose was found to suppress DMH-enhanced mitotic activity in the crypts of the descending colon during the initiation stage of carcinogenesis. This finding was correlated with a significantly lower incidence of adenocarcinomas in rats maintained on 5 or 15% cellulose throughout both the initiation and promotional stages.
Heitman
D W
DW
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
Ord
V A
VA
Hunter
K E
KE
Cameron
I L
IL
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002277:Carcinoma / Q000139:chemically induced*; D002455:Cell Division / Q000187:drug effects*; D002482:Cellulose; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004043:Dietary Fiber / Q000008:administration & dosage*; D004127:Dimethylhydrazines / Q000494:pharmacology*; D002149:Energy Intake; D008763:Methylhydrazines / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains
D004043:Dietary Fiber; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D002482:Cellulose; D019813:1,2-Dimethylhydrazine