Mechanism of Initiation of Liver Carcinogenesis by Dietary Imbalance
The role of diet in the modulation of carcinogenic process is known for several years. However, most of the emphasis was on how different macro and micro-constituents of diet can alter the biology of the system with respect to different carcinogens and modify the carcinogenic potential of the latter either by enhancing or diminishing the carcinogenicity to different organs. Recently, we and two other laboratories1–5 have shown that about 50% of rats develop hepatocellular carcinoma when fed a diet which is devoid of choline and low in methionine (CD) without any added carcinogen. The role of choline deficiency as a promoter in the carcinogenic process has been established6–7. The recent demonstration that CD alone without any added carcinogens caused liver cancer strongly suggests that CD both initiates and promotes, i.e. it is a carcinogenic regimen. This observation raised a puzzling question as to how the absence of something can cause initiation. A hypothesis has been proposed8 based on the following observations: (a) early hepatic nuclear lipid peroxidation which occurs in choline deficiency9 is followed closely by (b) DNA alteration10 and (c) liver cell proliferation11. These may represent the chain of events leading to initiation, promotion and eventually to cancer in this model where no known carcinogen is added.
KeywordsLipid Peroxidation Orotic Acid Liver Carcinogenesis Liver Cell Necrosis Choline Deficient Diet
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