Alcohol and other chemicals in the development of hepatocellular carcinoma.
A positive association between the incidence of hepatocellular carcinoma and the consumption of alcoholic beverages has been reported from some countries. The possible mechanistic nature of the association remains unclear, however. The effects of alcohol, as ethanol and as ethanol in various complex mixtures in the many different alcoholic beverages, were compared with the effects of well-known genotoxic and nongenotoxic or epigenetic carcinogens in carcinogenesis. There is no convincing evidence that alcohol can initiate the long multistep process of development of hepatocellular carcinoma. Thus, it appears that alcohol cannot be considered as a complete carcinogen. The effects of alcohol were also compared with known promoting agents for liver cancer. Although the available data are less clear, nevertheless it appears that alcohol cannot be considered as a bona fide promoting agent for liver cancer development. The most likely roles of alcohol in the genesis of liver cancer are: (1) to induce a well-known precancerous liver lesion, cirrhosis, and (2) to modulate, in an as yet ill-defined manner, the process of cancer development with known human carcinogenic influences such as hepatitis due to hepatitis B and hepatitis C viruses. Alcohol is well known to induce several enzymes in the liver and, thus, could theoretically modulate one or more steps in the carcinogenic process. Because alcohol has been found to alter cell membranes in well-defined ways and cell membrane changes, especially in the liver endoplastic reticulum, appear to be common in the later steps in liver cancer development, it is suggested that one site of alcohol action might be in the modulation of the biophysical composition of the liver endoplasmic reticulum and plasma membrane, favoring the cellular evolution to neoplasia.
Farber
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Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
D000818:Animals; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D000431:Ethanol; D006509:Hepatitis B; D006526:Hepatitis C; D006801:Humans; D008099:Liver / Q000473:pathology; D008108:Liver Diseases, Alcoholic; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology / Q000821:virology; D009153:Mutagens
D002273:Carcinogens; D009153:Mutagens; D000431:Ethanol