...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Exposure to anticancer drugs can result in transgenerational genomic instability in mice
【24h】

Exposure to anticancer drugs can result in transgenerational genomic instability in mice

机译：接触抗癌药可能会导致小鼠的转基因基因组不稳定

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The genetic effects of human exposure to anticancer drugs remain poorly understood. To establish whether exposure to anticancer drugs can result not only in mutation induction in the germ line of treated animals, but also in altered mutation rates in their offspring, we evaluated mutation rates in the offspring of male mice treated with three commonly used chemotherapeutic agents: cyclophosphamide, mitomycin C, and procarbazine. The doses of paternal exposure were approximately equivalent to those used clinically. Using single-molecule PCR, the frequency of mutation at the mouse expanded simple tandem repeat locus Ms6-hm was established in DNA samples extracted from sperm and bone marrow of the offspring of treated males. After paternal exposure to any one of these three drugs, expanded simple tandem repeat mutation frequencies were significantly elevated in the germ line (sperm) and bone marrow of their offspring. This observed trans-generational instability was attributed to elevated mutation rates at the alleles derived from both the exposed fathers and from the nonexposed mothers, thus implying a genome-wide destabiliza-tion. Our results suggest that paternal exposure to a wide variety of mutagens can result in transgenerational instability manifesting in their offspring. Our data also raise important issues concerning delayed transgenerational effects in the children of survivors of anticancer therapy.
机译：人类暴露于抗癌药物的遗传效应仍知之甚少。为了确定暴露于抗癌药是否不仅可以导致被治疗动物的生殖系中的突变诱导，而且可以导致其后代的突变率发生变化，我们评估了用三种常用化学治疗剂处理的雄性小鼠后代的突变率：环磷酰胺，丝裂霉素C和卡巴嗪。父亲暴露的剂量大约等于临床使用的剂量。使用单分子PCR，在从被治疗雄性后代的精子和骨髓中提取的DNA样品中，确定了小鼠扩展的简单串联重复序列基因座Ms6-hm的突变频率。父系接触这三种药物中的任何一种后，其后代的生殖系（精子）和骨髓中扩展的简单串联重复突变频率显着升高。这种观察到的跨代不稳定性归因于源于暴露的父亲和未暴露的母亲的等位基因的突变率升高，从而暗示了全基因组的不稳定。我们的结果表明，父亲暴露于多种诱变剂可导致其后代表现出跨代不稳定。我们的数据还提出了有关抗癌治疗幸存者孩子的延迟跨代效应的重要问题。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号