Comparison of the genetic effects of equimolar doses of ENU and MNU: While the chemicals differ dramatically in their mutagenicity in stem-cell spermatogonia, both elicit very high mutation rates in differentiating spermatogonia
Comparison of the genetic effects of equimolar doses of ENU and MNU: While the chemicals differ dramatically in their mutagenicity in stem-cell spermatogonia, both elicit very high mutation rates in differentiating spermatogonia
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DOI：
10.1016/j.mrfmmm.2006.11.003
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发表时间：
2007-03-01
影响因子：
2.3
通讯作者：
Russell, William L.
中科院分区：
文献类型：
--
作者：
Russell, Liane B.;Hunsicker, Patricia R.;Russell, William L.
在小鼠特异性位点试验中，在精子发生和精子形成的所有阶段的筛选中，比较了两种密切相关的化学物质，乙基亚硝基脲（ENU）和甲基亚硝基脲（XINU）在等摩尔和近等摩尔剂量下的致突变性、生殖和毒性效应。在干细胞精原细胞（SG）中，ENU的致突变性比MNU高一个数量级以上。在后SG阶段，这两种化学物质表现出高峰值的突变产量时，分化精原细胞（DG）和preleptotene精母细胞暴露。迄今为止，75 mg MNU/kg在该峰值间隔期间诱导的突变频率是任何单次暴露诱变处理（化学或辐射）诱导的最高突变频率，该处理允许暴露动物及其生殖细胞存活，估计每个基因组产生10个新突变。因此，干细胞和分化精原细胞在其敏感性MNU之间存在巨大差异，但这些阶段在其敏感性ENU.During减数分裂中期后的阶段，最高的突变产量是从暴露的spennatis，但对于这两种化学品，产量小于四分之一，从峰值间隔获得。仅在精子细胞中诱导大病变（LL）突变。虽然只有少数剩余的突变进行了分子分析，有相当多的证据，从最近的标记基因及其侧翼染色体区域的分子表征，大多数，如果不是全部，突变诱导的峰值敏感期不涉及标记位点以外的病变。SG后阶段的ENU和MNU处理都产生了大量的突变体，这些突变体被回收为镶嵌体，ENU的比例高于MNU。染色体畸变、对生殖细胞和动物的毒性、致畸性）显示，虽然XINU通常更有效，但当靶细胞是SG时，情况正好相反。(c)2006 Elsevier B. V.保留所有权利。
Mutagenic, reproductive, and toxicity effects of two closely related chemicals, ethyinitrosourea (ENU) and methyinitrosourea (XINU), were compared at equimolar and near-equimolar doses in the mouse specific-locus test in a screen of all stages of spermatogenesis and spermiogenesis. In stem-cell spermatogonia (SG), ENU is more than an order of magnitude more mutagenic than MNU. During post-SG stages, both chemicals exhibit high peaks in mutation yield when differentiating spermatogonia (DG) and preleptotene spermatocytes are exposed. The mutation frequency induced by 75 mg MNU/kg during this peak interval is, to date, the highest induced by any single-exposure mutagenic treatment - chemical or radiation - that allows survival of the exposed animal and its germ cells, producing an estimated 10 new mutations per genome. There is thus a vast difference between stem cell and differentiating spermatogonia in their sensitivity to MNU, but little difference between these stages in their sensitivity to ENU.During stages following meiotic metaphase, the highest mutation yield is obtained from exposed spennatids, but for both chemicals, that yield is less than one-quarter that obtained from the peak interval. Large-lesion (LL) mutations were induced only in spermatids. Although only a few of the remaining mutations were analyzed molecularly, there is considerable evidence from recent molecular characterizations of the marker genes and their flanking chromosomal regions that most, if not all, mutations induced during the peak-sensitive period did not involve lesions outside the marked loci. Both ENU and MNU treatments of post-SG stages yielded significant numbers of mutants that were recovered as mosaics, with the proportion being higher for ENU than for MNU.Comparing the chemicals for the endpoints studied and additional ones (e.g., chromosome aberrations, toxicity to germ cells and to animals, teratogenicity) revealed that while XINU is generally more effective, the opposite is true when the target cells are SG. (c) 2006 Elsevier B.V. All rights reserved.