Genotoxicity evaluation of pyrazinamide in mice

Pyrazinamide, an antituberculosis drug, was investigated for genotoxicity in mice, an in vivo rodent system. Three doses (125, 250 and 500 mg/kg bw corresponding to 5, 10 and 20 times the therapeutic dose respectively) were tested. The mitotic index and the frequency of chromosomal aberrations were analysed at three sample times (3, 6 and 24 h) after a single intraperitoneal treatment. The frequency of sperm shape abnormalities was also examined. The mitotic index showed a decrease in drug-treated animals compared with that recorded in the control set. The cells with chromosomal aberrations ranged from 4% to 8%. The maximum frequency of aberrations was found at the 3-h sample time. The frequency of sperm shape abnormalities showed a dose-related increase. These observations suggest pyrazinamide to be a weak genotoxicant at the doses tested.