EFFECT OF ALCOHOL ON GASTROINTESTINAL CELL REGENERATION AS A POSSIBLE MECHANISM IN ALCOHOL-ASSOCIATED CARCINOGENESIS

Chronic ethanol consumption is a major risk factor for oropharyngeal, esophageal, and rectal cancer. Because hyperregenerative gastrointestinal mucosa has an increased susceptibility towards chemical carcinogens and thus influences carcinogenesis, various studies have been performed to evaluate the effect of chronic ethanol consumption on mucosal cell turnover. In the rat, morphometric analysis showed that in chronically ethanol-fed rats the size of the basal cell nuclei of the oral mucosa from the floor of the mouth, the edge of the tongue, and the base of the tongue were significantly enlarged. The size of the basal cell layer was increased and the stratification of the cells was altered. The percentage of cells in S-phase of the cell cycle was significantly higher in ethanol-fed rats compared to controls. In addition, mucosal atrophy was found. Similar to the oropharynx, in the esophagus chronic ethanol consumption increased cell proliferation depending on salivary gland function, because only in the presence of the salivary glands was this stimulative effect of alcohol on cell turnover found. Subsequently, chronic ethanol ingestion significantly stimulated crypt cell production rate in the rectum, in an age-dependent manner. This hyperregeneration, which was only observed in the rectum but not in the remaining colon, was associated with an expansion of the proliferative compartment of the crypt. Such an expansion is correlated with increased risk for rectal cancer. In addition, crypt cell production rates in the rectal crypts can be correlated with mucosal acetaldehyde concentrations, underlining a toxic effect of acetaldehyde on the rectal mucosa that is answered by compansatory hyperregeneration. These data from the rat model could be confirmed in humans. In conclusion, chronic ethanol consumption leads to mucosal hyperregeneration in gastrointestinal mucosa associated with a high risk for cancer and may therefore be at least one mechanism by which alcohol exerts its cocarcinogenic effect.