Prospective epidemiologic studies have reported an increased risk of
rectal cancer following chronic
ethanol ingestion. The effect of
ethanol on chemically induced colorectal
carcinogenesis is controversial depending on the experimental conditions. In the present study the effect of chronic
ethanol administration on acetoxymethylmethylnitrosamine-induced
rectal cancer and the possible role of
acetaldehyde in this process were investigated. Chronic
ethanol administration resulted in an earlier occurrence of
rectal tumors in this animal model. Because the concomitant administration of
cyanamide, a potent
acetaldehyde dehydrogenase inhibitor, showed a positive trend toward increased incidences of
tumors,
acetaldehyde could be involved in the
ethanol-associated
carcinogenesis. To measure colonic
acetaldehyde, 12 chronically
ethanol-fed and control rats received an acute dose of
ethanol (2.5 g/kg body wt). The mucosal concentration of
acetaldehyde was significantly higher in the rectum compared with the cecum (198 +/- 23 vs. 120 +/- 23 nmoles.g colon-1, p less than 0.05), but was not affected by chronic
ethanol feeding. Furthermore, 6 germ-free rats had significantly lower
acetaldehyde concentrations in the rectum (84 +/- 11 vs. 234 +/- 33 nmoles.g colon-1, p less than 0.01) and in the cecum (59 +/- 13 vs. 121 +/- 33 nmoles.g colon-1, p less than 0.05) compared with 6 conventional animals, and this was paralleled by the number of fecal bacteria in the 2 intestinal segments. In addition, to determine the effect of chronic
ethanol feeding on colorectal cell turnover, 30 animals were pair-fed liquid diets. Using the metaphase-arrest technique, alcohol feeding induced rectal (19.1 +/- 2.0 vs. 9.1 +/- 1.8 cells.crypt-1.h-1, p less than 0.01), but not cecal (18.9 +/- 1.3 vs. 22.2 +/- 3.3 cells.crypt-1.h-1, p greater than 0.05) hyperregeneration. This was accompanied by an increase in the crypt proliferative compartment and increased mucosal
ornithine decarboxylase activity (63 +/- 18 vs. 22 +/- 6 pmoles.hr-1.mg
protein-1, p less than 0.05). The data show that chronic
ethanol ingestion accelerates chemically induced rectal
carcinogenesis and raise the possibility that
acetaldehyde probably generated through bacterial
ethanol oxidation may be involved in this process. The secondary hyperregeneration of the mucosa, observed after alcohol feeding, could by itself favour
carcinogenesis.