AIM: To investigate if azathioprine could reduce adenoma formation in ApcMin/+, a mouse model of sporadic intestinal tumorigenesis.METHODS:Azathioprine was administered via drinking water(estimated 6-20 mg/kg body wei...AIM: To investigate if azathioprine could reduce adenoma formation in ApcMin/+, a mouse model of sporadic intestinal tumorigenesis.METHODS:Azathioprine was administered via drinking water(estimated 6-20 mg/kg body weight per day)to ApcMin/+and wildtype mice.Control animals received vehicle only(DMSO)dissolved in drinking water.At 15wk of age all mice were sacrificed and intestines of ApcMin/+were harvested for evaluation of polyp number.Azathioprine induced toxicity was investigated by immunohistochemical analysis on spleens.RESULTS: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).CONCLUSION:We conclude that in the absence of inflammation,azathioprine does not affect intestinal tumorigenesis.展开更多
文摘AIM: To investigate if azathioprine could reduce adenoma formation in ApcMin/+, a mouse model of sporadic intestinal tumorigenesis.METHODS:Azathioprine was administered via drinking water(estimated 6-20 mg/kg body weight per day)to ApcMin/+and wildtype mice.Control animals received vehicle only(DMSO)dissolved in drinking water.At 15wk of age all mice were sacrificed and intestines of ApcMin/+were harvested for evaluation of polyp number.Azathioprine induced toxicity was investigated by immunohistochemical analysis on spleens.RESULTS: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).CONCLUSION:We conclude that in the absence of inflammation,azathioprine does not affect intestinal tumorigenesis.
