Cell proliferation and its evaluation in the colorectal mucosa: effect of ethanol

Colorectal cell turn over is affected by numerous factors including diets, alcohol consumption, smoking or age and is also significantly changed in certain mucosal diseases including benign and malignant tumors. Mucosal hyperregeneration is associated with an increased cancer risk since it increases the susceptibility of the mucosa towards the action of carcinogens. The measurement of colorectal mucosal regenerativity can be used for risk assessment in carcinogenesis. For the evaluation of colorectal regeneration in vivo and in vitro methods exist. The most accurate and elegant in vivo method is the metaphase arrest technique which is a dynamic measurement of cell turn over using vincristine to arrest metaphase figures. This method is limited to animals. In man, colorectal biopsies can be incubated with tritiated thymidine or with bromodeoxyuridine and thereafter the incorporation of the two compounds into DNA can be visualized by autoradiography or by immunohistology. More recent developments include the use of antibodies against certain proteins which are closely related to certain phases of the cell cycle and which are expressed in dividing cells. The most frequently used proteins are proliferative cellular nuclear antigen (PCNA) and Ki-67 which are visualized by immunohistology in routinely fixed histological specimens. Finally, in situ hybridization of histone H3 mRNA which is almost exclusively expressed during S-phase, has been established as an excellent method for the determination of colorectal cell regeneration. In conclusion, chronic alcohol consumption both in animals and in man leads to mucosal cellular hyperregeneration, possibly secondary to mucosal injury, most likely due to acetaldehyde. The acetaldehyde is produced mainly by fecal bacteria and may exert its toxicity by mechanisms still unknown, possibly involving a direct effect on DNA. The ethanol-associated mucosal hyperregeneration is closely related to carcinogenesis since chronic ethanol ingestion leads to an increased risk of cancer in the colorectum.