Mutagenic and genotoxic effect of hydroxyurea

Abstract

The hydroxyurea, a cytotoxic drug, is the mainly available therapeutical strategy for the treatment of sickle cell disease. This study aimed to evaluate the mutagenic and genotoxic potential of the hydroxyurea through the Salmonella/Microsome assay and micronucleus test in peripheral blood of mice. The doses were evaluated at 29.25-468 μmol/plate in Salmonella/Microsome assay in presence and absence of metabolic activation the drug. In the micronucleus test the doses were evaluated at 12.5; 25; 50; 75 and 100 mg/kg. The results show that hydroxyurea present mutagenic activity in TA98 and TA100 in doses above 117 μmol/plate and 234 μmol/plate respectively. The drug induced a significant increase in the frequency of micronuclei in reticulocytes of mice at concentrations of 50, 75 and 100 mg/kg, compared to negative control (water). These results demonstrated the mutagenic and genotoxic potential of hydroxyurea.

Keywords: genotoxicity; hydroxyurea; micronucleus test; mutagenicity.

Figure 1

Average frequency of micronucleated reticulocytes (MNRET) and standard deviation of 1000 cells obtained from mice treated with water (negative control) and hydroxyurea. ^*P<0.05 (compared to negative control), ^**P<0.05 (compared to doses of 12.5 and 25 mg/kg), ^***P<0.05 (compared to the doses 12.5, 25 and 50 mg/kg).

Figure 2

Average frequency of micronucleated reticulocytes (MNRET) and standard deviation of 1000 cells from mice treated with cyclophosphamide (positive control), CMC/Tween (negative control) and water (control white). ^*P<0.05.