Comparison of the effect of hydroxyurea and methotrexate on DNA fragmentation at various reaction conditions

Using the changes in DNA breakage as a marker of DNA damage, the direct action of hydroxyurea (HU) and methotrexate (MTX) on DNA was examined. The experimental design was to expose isolated DNA to HU and MTX alone or HU and MTX with accelerators of free radical reaction (H2O2, Fe..) and to determine DNA fragmentation assessed by electrophoresis. The results indicated that HU can damage DNA, but to demonstrate this ability it needs H2O2, Fe.. or prolonged incubation in solution. Unlike HU, MTX with H2O2 was ineffective; MTX with Fe.. at certain degree protected DNA against lesions induced by Fe.. alone. It is concluded that despite several common features of HU- and MTX-induced toxic side-effects in the cells suggesting interference of these drugs with free radical reactions, their direct effect on DNA under oxidizing conditions is quite different at least at the concentrations used by us.