Effects of dietary fiber on the rat intestinal mucosa exposed to low doses of a carcinogen.
BACKGROUND
Changes in morphological and immunohistochemical parameters were studied in the rat intestinal mucosa exposed to low doses of a carcinogen and administered with dietary fibers.


METHODS
Tumors were induced by five subcutaneous injections of 1,2-dimethylhydrazine, 10 mg/kg rat, once a week. Rats were fed a semi-synthetic fiber-free diet (control) or a high-fiber diets (15%) derived from cellulose, tomato peels or white grape. The rats were sacrificed 24 weeks after the first carcinogen's injection. The ileum, colon and tumors were removed for the study. Areas of the mucosal stroma and of lymph infiltrations, and mitotic index were studied along with morphological parameters. Immunohistochemical parameters included determination of Ki-67 proliferating protein and apoptotic index.


RESULTS
Areas of the stroma in colon tumors increased in rats fed tomato peels. Changes in areas of lymphoid infiltrates were related to the type of diet and tumor presence. Lymphoid infiltrations were found to be highly developed in the colon area close to tumors, especially in rats fed the white-grape diet. Mitotic index and Ki-67 protein increased significantly in the colon area close to a tumor and in tumors themselves without any relation to the fiber varieties consumed. Changes in the rate of apoptosis were not related to the preventive effect of diets: apoptotic index was high in tumors obtained from rats fed the high-cellulose diet with high tumor-preventive effects and also from rats fed the high-tomato-peel diet with low tumor-preventive effects.


CONCLUSIONS
No morphological changes were found in the ileum of rats exposed to a carcinogen and fed different dietary fibers. In the colon, a carcinogen even in low concentrations inhibited the lymphoid system in the mucosa located far from the tumor or close to the tumor. An increase in the proliferation rate in the colon close to the tumor may reflect the development of precanceromatous processes or may be related to the effect of growth factors expressed by tumor cells. Finding adenoma-like dysplasia near tumors may be possible in early stages of the development of new tumors. In addition, activation of the lymphoid system of the colon following consumption to specific dietary fiber may be a mechanism by which fiber protect against cancer.
Madar
Z
Z
School of Nutrition Sciences, Koret School of Veterinary Medicine, Faculty of Agricultural, Hebrew University of Jerusalem, Rehovot, Israel.
Gurevich
P
P
Ben-Hur
H
H
Ben-Arie
A
A
Berman
V
V
Sandler
B
B
Timar
B
B
Tendler
Y
Y
Zinder
O
O
Stark
A
A
Zusman
I
I
D019813:1,2-Dimethylhydrazine / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002273:Carcinogens / Q000008:administration & dosage*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004043:Dietary Fiber / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D002273:Carcinogens; D004043:Dietary Fiber; D019394:Ki-67 Antigen; D019813:1,2-Dimethylhydrazine