Effects of chronic ethanol feeding on chemical hepatocarcinogenesis and retinoid metabolism.

摘要

Chronic and excessive alcohol consumption is a significant risk factor for liver cancer and it is known to interfere with retinoid metabolism. Even though ethanol is not a carcinogen by itself, its role as a possible promoter in the carcinogenesis process has been suggested by several experimental investigations. However, due to the complex effects and interactions of ethanol in a biological system, it has been difficult to demonstrate the promoting role of ethanol in a chemical carcinogenesis process. A lack of in vivo evidence, where ethanol could be observed as acting as a promoter of hepatocarcinogenesis, motivated the present thesis work.; This research investigated whether chronic and excessive ethanol treatment can act as a possible promoter for hepatic carcinogenesis in a diethylnitrosamine initiated animal model, by studying the role of cell proliferation and apoptosis. We observed in the ethanol fed groups lower number of altered hepatic foci as well as lower protein levels of hepatic Cyclin D1 and lower hepatocyte proliferation labeling. This would create an adequate environment for the selection of foci with a resistant phenotype that will eventually evolve into neoplastic lesions.; In this thesis research we also found higher concentrations of hepatic retinoic acid (RA) and retinol levels in the ethanol fed rats compared to the non-ethanol fed rats, which could suggest in this model a role of ethanol in the biosynthesis of RA with accumulation of retinol.