Golos B, Malec J
Department of Biochemistry, Institute of Hematology, Warsaw, Poland.
Neoplasma. 1991;38(6):559-64.
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.
以DNA断裂的变化作为DNA损伤的标志物，研究了羟基脲（HU）和甲氨蝶呤（MTX）对DNA的直接作用。实验设计是将分离的DNA单独暴露于HU和MTX，或与自由基反应促进剂（H2O2、Fe...）一起暴露于HU和MTX，并通过电泳测定DNA片段化情况。结果表明，HU可损伤DNA，但要证明这种能力，它需要H2O2、Fe...或在溶液中长时间孵育。与HU不同，MTX与H2O2一起无效；MTX与Fe...在一定程度上可保护DNA免受单独Fe...诱导的损伤。结论是，尽管HU和MTX在细胞中诱导的毒副作用有几个共同特征，提示这些药物干扰自由基反应，但在氧化条件下，它们对DNA的直接作用至少在我们使用的浓度下有很大差异。
