Alcohol is a well-recognized hepatic carcinogen. Alcohol is metabolized into genotoxic
acetaldehyde in hepatocytes, which is catalyzed by aldehyde dehydrogenase 2 (ALDH2).
The detailed underlying mechanisms of alcohol-related hepatocellular carcinoma (HCC)
remains unclear, at least partially, due to the absence of appropriate experimental
models. Current studies suggest that rodents are not good models of the most common
liver diseases that trigger HCC including alcoholic liver injury. We hypothesize that
ethanol could induce transformation of immortalized normal liver cells, which may
serve as a versatile tool for studying alcoholic HCC. Besides, we believe that knockout
of ALDH2 will help to shorten the time course of transformation, as ALDH2 deficiency
will significantly increase the accumulation of acetaldehyde in hepatocytes. Using
this model, the dynamic changes of carcinogenesis-related molecular events could be
easily examined. Furthermore, the transformed cells isolated from soft agar could
be inoculated to mice for studying invasion, metastasis, and also for screening prophylactics.