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Dietary Folate Suppresses DMH-Induced Colon Carcinogenesis in a Rat Model and Affects DMH-Induced Expression of Four DNA Repair Enzymes

Author:
Sadik, Nermin A. H., Shaker, Olfat G.
Source:
Nutrition and cancer 2012 v.64 no.8 pp. 1196-1203
ISSN:
1532-7914
Subject:
Chinese hamsters, DNA repair, X-radiation, animal models, body weight, carcinogenesis, colon, colorectal neoplasms, diet, enzymes, etiology, folic acid, gene expression regulation, genes, humans, proliferating cell nuclear antigen, protective effect, rats, survival rate
Abstract:
This study investigated the potential role of folate in the dimethylhydrazine (DMH) colon cancer model in male Wistar rats. For induction of colon cancer, group 1 rats were injected subcutaneously with 30 mg DMH/kg body weight weekly for 30 wk. Group 2 received DMH vehicle. Group 3 rats received DMH as in Group 1 but their diet was supplemented with 8 mg folate/kg diet. Group 4 was fed diet supplemented with 8 mg folate/kg diet. Upregulation of DNA damage repair genes Apurinic/apyrimidinic endonuclease 1, X-ray repair complementing defective repair in Chinese hamster cells 5, 8-oxoguanine-DNA glycosylase, and proliferating cell nuclear antigen, associated with a reduction of folic acid level was observed in colons of DMH group. Reductions of these gene upregulations and a significant increase of colonic folic acid level occurred in the DMH group supplemented with folic acid and this group also had significant inhibition of tumor incidence, normal survival rate and histologically nearly normal colonic architecture. It can be concluded that folate supplementation exerts a potent protective effect on rat colon carcinogenesis via significant modulation of DNA repair, providing a mechanism by which it plays a role in the etiology of human cancer.
Agid:
263348