Azathioprine does not reduce adenoma formation in a mouse model of sporadic intestinal tumorigenesis

摘要

To investigate if azathioprine could reduce adenoma formation in Apc(Min/+) , a mouse model of sporadic intestinal tumorigenesis. Azathioprine was administered via drinking water (estimated 6-20 mg/kg body weight per day) to Apc(Min/+) and wildtype mice. Control animals received vehicle only (DMSO) dissolved in drinking water. At 15 wk of age all mice were sacrificed and intestines of Apc(Min/+) were harvested for evaluation of polyp number. Azathioprine induced toxicity was investigated by immunohistochemical analysis on spleens. All azathioprine treated mice showed signs of drug-associated toxicity such as weight loss and development of splenic T-cell lymphomas. Although this suggests that the thiopurine concentration was clearly in the therapeutic range, it did not reduce tumor formation (48 ± 3.1 adenomas vs 59 ± 5.7 adenomas, P = 0.148). We conclude that in the absence of inflammation, azathioprine does not affect intestinal tumorigenesis