Effect of activity-stress on experimental rat colon carcinogenesis: early histopathologic changes and colon tumor...

The effect of stress on experimental colon carcinogenesis was investigated in the rat by adapting the activity-stress ulcerogenesis model to the 1,2-dimethylhydrazine (DMH) rat colon carcinogenesis model. Activity-stress was applied intermittently (normal housing conditions alternated with activity-stress conditions on an equal time basis) to DMH-injected rats either throughout the experiment (AS-DMH) or following completion of DMH injections (DMH-AS). The AS-DMH treatment was associated with reduced colonic tumor induction compared with controls, as was to a lesser degree with DMH-AS condition. In a separate study, the early histopathologic effects on the colon of a single DMH injection, an activity-stress treatment, or the combination of both DMH and activity-stress treatments were compared with those of controls. Activity-stress moderated DMH-induced increases in colonic epithelial cell proliferation and nuclear hyperchromia when compared with DMH treatment alone. The findings of activity-stress-associated protection on colon tumor induction and the concordance of these results with quantitative early histopathologic alterations demonstrate that in the rat activity-stress exerts a protective influence in colon carcinogenesis. In addition, these results suggest further that risk modifiers of colon cancer can be assessed in short-term studies that quantify early histopathologic alterations.