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Effect of Age on Susceptibility to Azoxymethane-Induced Colonic Aberrant Crypt Foci Formation in C57BL/6JNIA Mice

¹ Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
² Department of Family Medicine and Community Health, Tufts University School of Medicine, Boston, Massachusetts.
³ Department of Biological Science, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts.
⁴ Department of Pathology, Sackler Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts.

To determine the effect of age on susceptibility to azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and its underlying mechanism, young and old mice were injected with AOM weekly for 4 or 5 weeks and euthanized 5 or 6 weeks later. Given the same (12 or 15) mg/kg body weight dose of AOM, old mice had significantly more ACF than young mice. However, given the same total dose of AOM (to avoid confounding effect of higher dose to heavier old mice), at a low total dose (1.5 mg) there was no age difference, but at higher total doses (1.8 and 2.2 mg) young mice had significantly more ACF than old mice. These results indicate that the age-related susceptibility to AOM differs depending on whether administration of the carcinogen is based on weight or total dose. These age differences are not due to variations in cyclooxygenase-2 expression, cell proliferation, or AOM hydroxylase activity.