Chlorambucil effectively induces deletion mutations in mouse germ cells.
Chlorambucil effectively induces deletion mutations in mouse germ cells.
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Chlorambucil 可有效诱导小鼠生殖细胞缺失突变。
DOI：
10.1073/pnas.86.10.3704
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发表时间：
1989
影响因子：
11.1
通讯作者：
Shelby,MD
中科院分区：
文献类型：
--
作者：
Russell,LB;Hunsicker,PR;Cacheiro,NL;Bangham,JW;Russell,WL;Shelby,MD
研究发现，化疗药物苯丁酸氮芥比 X 射线或迄今为止研究的任何化学物质更有效地诱导小鼠种系突变，这些突变似乎是缺失或其他结构变化。在不同雄性生殖细胞阶段暴露于10-25 mg/kg苯丁酸氮芥后，研究了涉及七个特定位点的突变诱导。总共对 60,750 个后代进行了评分。精原干细胞的突变率与对照值相比没有显着增加；这种负面结果不能归因于选择性消除突变细胞。然而，在治疗后的干细胞阶段明显诱导了突变，其中发现了突变反应的显着变化。早期精子细胞暴露后出现最大产量，10 mg/kg 组中大约 1% 的后代携带特定位点突变。苯丁酸氮芥的阶段反应模式与迄今为止在特定位点测试中研究的所有其他化学品的阶段反应模式不同。迄今为止，除一种以外，所有由苯丁酸氮芥在后干细胞阶段诱导的测试突变均已通过遗传、细胞遗传学和/或分子标准证明是缺失或其他结构变化。删除突变最近对于分子作图和基因组区域的结构功能相关性很有用。为了以最高频率产生假定的大病变种系突变，苯丁酸氮芥可能是首选的诱变剂。
The chemotherapeutic agent chlorambucil was found to be more effective than x-rays or any chemical investigated to date in inducing high yields of mouse germ-line mutations that appear to be deletions or other structural changes. Induction of mutations involving seven specific loci was studied after exposures of various male germ-cell stages to chlorambucil at 10-25 mg/kg. A total of 60,750 offspring was scored. Mutation rates in spermatogonial stem cells were not significantly increased over control values; this negative result is not attributable to selective elimination of mutant cells. Mutations were, however, clearly induced in treated post-stem-cell stages, among which marked variations in mutational response were found. Maximum yield occurred after exposure of early spermatids, with approximately 1% of all offspring carrying a specific-locus mutation in the 10 mg/kg group. The stage-response pattern for chlorambucil differs from that of all other chemicals investigated to date in the specific-locus test. Thus far, all but one of the tested mutations induced by chlorambucil in post-stem-cell stages have been proved deletions or other structural changes by genetic, cytogenetic, and/or molecular criteria. Deletion mutations have recently been useful for molecular mapping and for structure-function correlations of genomic regions. For generating presumed large-lesion germ-line mutations at highest frequencies, chlorambucil may be the mutagen of choice.