Investigation into the mutagenic activity of azathioprine (Imuran) in different test systems.

The chromosome-damaging effect of azathioprine (Imuran) was investigated in the micronucleus test with mice and rats, in the pertussis-stimulated lymphocyte metaphase test with rabbits, and in children on azathioprine therapy. In the micronucleus test, there was a dose-dependent increase in the number of cells with micronuclei. The dose was given twice in 24 h, i.p., 25, 50 and 100 mg/kg body weight for mice, and 50, 100 and 200 mg/kg for rats. In the lymphocyte test, a dose of 5 and 20 mg azathioprine per kg body weight was given orally to rabbits on three successive days after pertussis injection. Compared with treatment in the control group these treatments induced a significantly increased number of cells with chromosomal abnormalities. These results were confirmed in lymphocyte cultures of children on long-term azathioprine therapy after kidney transplantation, where an increase in the number of structural chromosomal abnormalities was observed.