Chemoprevention of spontaneous intestinal adenomas in the adenomatous polyposis coli Min mouse model with aspirin.

Abstract

Colorectal cancer is a significant source of morbidity and mortality in the United States and other Western countries. Epidemiological and experimental data indicate that regular use of aspirin reduces colon cancer risk. This study was designed to determine if aspirin would significantly inhibit gastrointestinal tumor formation in a mouse model of familial adenomatous polyposis. Six-week-old male and female C57BL/6J +/+ (control) and C57BL/6J ApcMin/+ (Min) mice were fed either a control AIN-76A diet or one supplemented with 250 or 500 parts per million (ppm) aspirin (n = 6 per group) for 7 weeks. All of the Min mice, but no control mice, developed gastrointestinal tumors. Aspirin significantly reduced tumor multiplicity (number of tumors per mouse) in the small intestine, but not the colon, from an average of 35.8 tumors per mouse (control diet) to 16 and 18.5 tumors per mouse with 250 and 500 ppm aspirin, respectively. Total tumor load (sum of tumor diameters per mouse) was also significantly reduced, from 93.2 mm in total diameter to 40. 4 and 45.0 mm with 250 and 500 ppm aspirin, respectively. Results were not significantly different because of sex or aspirin dose. High doses of aspirin are effective chemopreventive agents in a mouse model of spontaneous intestinal tumor formation.