Inhibitory effects of trientine, a copper-chelating agent, on induction of DNA strand breaks in kidney cells of long-Evans Cinnamon (LEC) rats
Inhibitory effects of trientine, a copper-chelating agent, on induction of DNA strand breaks in kidney cells of long-Evans Cinnamon (LEC) rats
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DOI：
10.1538/expanim.54.403
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发表时间：
2005-10-01
影响因子：
2.4
通讯作者：
Okui, T
中科院分区：
文献类型：
--
作者：
Hayashi, M;Miyane, K;Okui, T
在Long-Evans Cinnamon（LEC）大鼠（一种人类Wilson病动物模型）中研究了Trientine（一种特异性铜螯合剂）治疗对铜蓄积和DNA链断裂诱导的影响。从12到18周龄，LEC大鼠肾脏中铜的积累呈年龄依赖性。当LEC大鼠从10周龄开始接受曲恩汀治疗时，肾脏铜含量未增加，并维持在与4周龄LEC大鼠相同的水平。彗星试验的DNA单链断裂（SSBs）的量的估计表明，DNA的SSBs诱导大量的LEC大鼠肾皮质细胞在12周龄左右，SSBs的量增加，在年龄依赖性的方式从12至18周龄。当LEC大鼠从10周龄开始接受曲恩汀给药时，观察到的DNA损伤细胞数量减少，表明在曲恩汀给药期间DNA SSB的诱导受到抑制和/或SSB得到修复。结果表明，LEC大鼠肾细胞中DNA的SSB在肝损伤的临床体征发生之前被诱导，并且用曲恩汀治疗LEC大鼠减少了DNA链断裂的数量。
The effects of treatment with trientine, a specific copper-chelating agent, on the accumulation of copper and induction of DNA strand breaks were investigated in Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson's disease. Copper accumulated in the kidneys of LEC rats in an age-dependent manner from 12 to 18 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, renal copper contents did not increase and were maintained at the same levels as those in 4-week-old LEC rats. Estimation of the amounts of DNA single-strand breaks (SSBs) by comet assay showed that SSBs of DNA were induced in a substantial population of LEC rat renal cortex cells around 12 weeks of age and that the amounts of SSBs increased in an age-dependent manner from 12 to 18 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, the observed number of cells with DNA damage decreased, suggesting that induction of SSBs of DNA was inhibited and/or SSBs were repaired during the period of treatment with trientine. The results show that SSBs of DNA in LEC rat kidney cells are induced prior to occurrence of clinical signs of hepatic injury and that treatment of LEC rats with trientine decreases the number of DNA strand breaks.