Genotoxic and cytotoxic effect of deferasirox

The aim of this study was to determine by various tests whether deferasirox has potential genotoxicity. Deferasirox is one of iron chelators which used in the treatment of iron storage disease (hemochromatosis) that occurs for various reasons. Exjade that commercial form of deferasirox was used as the test substance in this study. Peripheral lymphocytes of healthy individuals were used for sister chromatid exchange (SCE) and chromosome aberration (CA) tests, under absence or presence of in vitro metabolic activator (S9 mix). In addition chromosomal aberration test in rat bone marrow cells were also performed. The results of the study showed that the findings from this study are examined that SCE frequency was increased significantly (P<0.05) in the peripheral lymphocytes at the lowest dose of test substance in 24 hours, and all doses in 48 hours. Under the presence of S9 mix, there was a significant increase in SCE at only the highest concentration (40 mg/ml). Furthermore, except one concentration (10 mg/ml, 24 h) deferasirox significantly increased the number of chromosomal abnormalities regardless of application times and presence of S9 mix. Similarly, the highest two doses (500 and 1000 mg/kg) of test substance increased the CA frequency statistically in rats bone marrow cells only at 12 hours application period. However, none of the significant findings was detected in 24-hour period of the same application. Frequency of chromosomal abnormalities per cell (CA/cell) also showed consistency with the CA frequency. In general terms, deferasirox reduced in vitro proliferation index (PI), and mitotic index (MI) values a few exceptions. The MI values were significant only. Test substance increased mitotic index in rat bone marrow cells except one dose (20 mg/kg, 24 hours). These findings showed similarity with in vitro MI values obtained from S9 mix application.