Off-campus WSU users: To download campus access dissertations, please use the following link to log into our proxy server with your WSU access ID and password, then click the "Off-campus Download" button below.

Non-WSU users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

Access Type

WSU Access

Date of Award

December 2011

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Nutrition and Food Science

First Advisor

Ahmad R. Heydari

Abstract

Folate, an essential water soluble vitamin has been implicated in the etiology of many types of cancer especially colorectal cancer. Folate deficiency has been reported to incapacitate DNA repair pathways and thereby affect the genomic stability. Our lab has reported previously and here again through this research that folate deficiency affects the DNA damage inducibility of base excision repair pathway. Our study shows the differential effect folate deficiency has on the expression of the genes involved in this pathway. Further, our study shows the increase in preneoplastic lesions in the colon of mice exposed to folate deficiency in response to dimethylhydrazine, a colon and liver carcinogen. This study further supports our findings from previous studies from our lab that folate deficiency increases the susceptibility to cancer by deregulating DNA repair pathways, base excision repair in this scenario. Similarly, methionine restriction also, increases accumulation of preneoplastic lesions and incapacitates base excision repair in mice exposed to dimethylhydrazine. Since methionine restriction has shown to produce beneficial effects in laboratory rodents when the animals are exposed to long term restrictions, it would be interesting to put our animal models on methionine restriction and folate deficient diets for longer periods to test whether long term adaptations would bring about any beneficial effects