Our observation that rats kept on a diet deficient in choline and methionine (CMD) develop hepatocellular carcinoma (23/45) within 13 to 24 months while the control group on the same diet but with added choline chloride (0.8%) develop no neoplastic or preneoplastic lesions has prompted us to explore this phenomena in greater depth. We also found that nuclear lipid peroxidation and DNA damage occurs very early in the liver of rat ingesting CMD diet. That dietary deficiency alone without any added carcinogen might cause cancer has a profound significance not only from the mechanistic but also from human point of view, since methionine is one of the amino acids present in relatively low amounts in many plant proteins. The objectives of this proposal are (i) to study the possible role of methionine in CMD induced liver carcinogenesis and (ii) to probe into the mechanism by which CMD diet produces hepatocellular carcinoma. The role of lipid peroxidation and DNA damage, biochemical alterations induced by feeding CMD diet, in the carcinogenic process will be explored in respect to initiation, promotion and progression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041537-02
Application #
3182138
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1986-03-01
Project End
1989-02-28
Budget Start
1987-03-01
Budget End
1988-02-29
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Toronto
Department
Type
DUNS #
259999779
City
Toronto
State
ON
Country
Canada
Zip Code
M5 1S8
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Ghoshal, A K; Rushmore, T H; Buc-Calderon, P et al. (1990) Prevention by free radical scavenger AD5 of prooxidant effects of choline deficiency. Free Radic Biol Med 8:3-7
Ghoshal, A; Roomi, M W; Ahluwalia, M et al. (1988) Glutathione and enzymes related to free radical metabolism in liver of rats fed a choline-devoid low-methionine diet. Cancer Lett 41:53-62
Ghoshal, A K; Rushmore, T H; Farber, E (1987) Initiation of carcinogenesis by a dietary deficiency of choline in the absence of added carcinogens. Cancer Lett 36:289-96
Rushmore, T H; Ghazarian, D M; Subrahmanyan, V et al. (1987) Probable free radical effects on rat liver nuclei during early hepatocarcinogenesis with a choline-devoid low methionine diet. Cancer Res 47:6731-40
Ghoshal, A K; Laconi, E; Willemsen, F et al. (1987) Modulation of calcium by the carcinogenic process in the liver induced by a choline-deficient diet. Can J Physiol Pharmacol 65:478-82