Site specific reduction of colon cancer incidence, without a concomitant reduction in cryptal cell proliferation, in 1,2-dimethylhydrazine treated rats by diets containing 10% pectin with 5% or 20% corn oil

Abstract

The effects of specific dietary interventions on incidence of carcinogen-induced cancer and on cryptal cell proliferation in areas of the colon located either over aggregates of lymphoid nodules (ALN) or away from ALN was investigated. Groups of dimethylhydrazine (DMH) treated rats or non-DMH-treated rats were fed a basal AIN-76 diet less fiber of any type, or the basal fiber free diet supplemented with 10% pectin and with 5%, 10%, or 20% corn oil. The adenocarcinoma (AC) incidence was determined in regions of the colon, i.e. ascending, descending, descending over the ALN and descending away from the ALN. The results indicate that: (i) factors associated with ALN promote AC formation, (ii) dietary modifications (addition of pectin and of 20% corn oil to the diet) each cause significant site specific suppression of AC incidence, (iii) DMH-treatment rendered crypts non-responsive to the suppression of cryptal cell proliferation which occurred in the rats not treated with DMH (suggestive of a DMH-induced loss in the regulation of cell proliferation) and (iv) reduction of AC incidence was not always accompanied by reduction in crypt cell proliferation. Studies of intervention procedures designed to prevent colon cancer should take into account the colon site specific tumorigenic response to the preventive agent and should not rely on a single biomarker to predict the efficacy of the intervention.