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Published on: September 11, 2012
Azathioprine does not reduce adenoma formation in a mouse model of sporadic intestinal tumorigenesis
Mattheus C B Wielenga1, Jooske F van Lidth de Jeude1, Sanne L Rosekrans1
1Mattheus CB Wielenga, Jooske F van Lidth de Jeude, Sanne L Rosekrans, Alon D Levin, Monique Schukking, Geert RAM D'Haens, Jarom Heijmans, Vanesa Muncan, Gijs R van den Brink, Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105BK Amsterdam, The Netherlands.
Aim:
To investigate if azathioprine could reduce adenoma formation in Apc(Min/+) , a mouse model of sporadic intestinal tumorigenesis.
Methods:
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.
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.
