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Investigation into the mutagenic activity of azathioprine (Imuran) in different test systems
Abstract:
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.
Insights
Azathioprine (Imuran) demonstrated chromosome-damaging effects in animal models and humans. Studies showed a dose-dependent increase in micronuclei and chromosomal abnormalities, indicating genotoxicity.
Area of Science:
- Toxicology
- Genetics
- Pharmacology
Background:
- Azathioprine (Imuran) is an immunosuppressive drug.
- Understanding its genotoxic potential is crucial for patient safety.
Purpose of the Study:
- To evaluate the chromosome-damaging effects of azathioprine.
- To assess azathioprine's genotoxicity in vivo and in vitro.
Main Methods:
- Micronucleus test in mice and rats.
- Pertussis-stimulated lymphocyte metaphase test in rabbits.
- Analysis of lymphocyte cultures from children on azathioprine therapy.
Main Results:
- A dose-dependent increase in micronuclei was observed in rodents.
- Significant increases in chromosomal abnormalities occurred in rabbits.
- Elevated structural chromosomal abnormalities were found in children receiving long-term azathioprine therapy.
Conclusions:
- Azathioprine exhibits chromosome-damaging properties.
- The findings suggest azathioprine is a genotoxic agent.
- These results highlight potential risks associated with azathioprine use.