The effects of diet and ionizing radiation on azoxymethane induced colon carcinogenesis

Abstract

The ability of ionizing radiation to enhance colon carcinogenesis and the role of diet in this process has not been documented. We hypothesized that radiation would enhance the formation of aberrant crypt foci, ACF, known precursor lesions to colon cancer, by suppressing apoptosis and upregulating proliferation in colonocytes. Diets contained a combination of fish oil or corn oil and either pectin or cellulose. We exposed 40 male Sprague-Dawley rats to 1 Gy ionizing radiation (1 GeV Fe) 10 d prior to injection with AOM. Colons were resected at the promotion stage of carcinogenesis (7 wk post initial injection) and assayed for ACF and apoptosis. Radiation treatment increased (P=0.0327) the incidence of high multiplicity ACF (foci with four or more aberrant crypts) and decreased (P=0.0340) the apoptotic index compared to non-irradiated rats. Radiation also resulted in an increase (P<0.0001) in the proliferative index compared to the nonirradiated rats. The fish oil containing diets resulted in fewer (P=0.0002) high-multiplicity ACF compared to the corn oil treatment. Dietary pectin significantly increased (P=0.0204) the apoptotic index compared to cellulose treatment. These data suggest that ionizing radiation can work synergistically with AOM and increase the formation of high-multiplicity ACF, upregulate cellular proliferation and decrease apoptosis in colonocytes. The data also suggest that diets containing fish oil and pectin may protect against colon cancer by increasing apoptosis and reducing the formation of high multiplicity ACF.