Ochi T
Department of Environmental Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Mutat Res. 1989 Aug;213(2):243-8. doi: 10.1016/0027-5107(89)90156-5.
The effects of iron chelators and glutathione (GSH) depletion on the induction of chromosomal aberrations by tert-butyl hydroperoxide (t-BuOOH) were investigated in cultured Chinese hamster V79 cells. t-BuOOH in a concentration range of 0.1-1.0 mM induced chromosomal structural aberrations, consisting mainly of chromatid gaps and breaks, in a dose-dependent fashion. The divalent iron chelator o-phenanthroline almost completely suppressed the formation of chromosomal aberrations while the trivalent chelator desferrioxamine was less effective. GSH depletion did not affect the formation of chromosomal aberrations and DNA single-strand breaks (ssb) by t-BuOOH. DNA ssb by 0.5 mM t-BuOOH were repaired within 60 min of treatment in both GSH-depleted (GSH-) and non-depleted (GSH+) cells. In contrast, chromosomal aberrations increased a little during the 60 min after treatment in both GSH- and GSH+ cells. The aberrations were then repaired in GSH+ cells but those in GSH- cells were maintained to a great extent during 20 h of post-treatment incubation. These results indicate that divalent iron mediates the induction of chromosomal aberrations by t-BuOOH. That t-BuOOH-induced chromosomal aberrations remain even after DNA ssb were repaired suggests involvement of other lesions than DNA ssb in the formation of chromosomal aberrations by the hydroperoxide.
在培养的中国仓鼠V79细胞中，研究了铁螯合剂和谷胱甘肽（GSH）耗竭对叔丁基过氧化氢（t-BuOOH）诱导染色体畸变的影响。浓度范围为0.1-1.0 mM的t-BuOOH以剂量依赖的方式诱导染色体结构畸变，主要包括染色单体间隙和断裂。二价铁螯合剂邻菲罗啉几乎完全抑制了染色体畸变的形成，而三价螯合剂去铁胺的效果较差。GSH耗竭不影响t-BuOOH诱导的染色体畸变和DNA单链断裂（ssb）的形成。在GSH耗竭（GSH-）和未耗竭（GSH+）的细胞中，0.5 mM t-BuOOH诱导的DNA ssb在处理后60分钟内均可修复。相反，在处理后的60分钟内，GSH-和GSH+细胞中的染色体畸变均略有增加。随后，GSH+细胞中的畸变得到修复，但GSH-细胞中的畸变在处理后20小时的孵育过程中在很大程度上得以维持。这些结果表明，二价铁介导了t-BuOOH诱导的染色体畸变。即使DNA ssb得到修复，t-BuOOH诱导的染色体畸变仍然存在，这表明在过氧化物诱导染色体畸变的过程中，除了DNA ssb之外，还涉及其他损伤。
