Allen J W, Liang J C, Carrano A V, Preston R J
Mutat Res. 1986 Jan-Mar;167(1-2):123-37. doi: 10.1016/0165-1110(86)90013-8.
80 papers published between 1970 and 1984 were evaluated for results pertaining to chemical-induced aneuploidy in mammalian male germ cells. Diverse assays and end points were represented. The assays considered to involve direct measures of aneuploidy were based upon chromosome counts in premeiotic, meiotic, and embryonic cells, and the male pronucleus, or upon phenotypic expression of X-linked genetic markers. Assays in which indirect measures were interpreted as evidence for aneuploidy included those primarily assessing chiasma frequencies, univalent frequencies, and spermatid/sperm sex chromosome body counts. An initial screening to reject studies with insufficient data and those which did not involve a single chemical test agent led to the elimination of 39 papers from further review. The remaining 41 papers reported effects from 46 different chemicals. These papers were rigorously assessed for adequacy of experimental protocols, relevance of end points as direct measures of aneuploidy, and completeness of data presentation and statistical analysis. Criteria specific to each assay were also considered. 4 chemical tests were considered to provide reliable positive or negative aneuploidy data. Cyclophosphamide and chloral hydrate each caused metaphase II hyperploidy when injected into mice. Very limited analyses of trenimon and isoniazid provided negative results. Test findings for 44 chemicals were viewed as inconclusive. It was concluded that standardization of tests to evaluate chemical-induced aneuploidy in male germ cells and the application of these tests towards increasing the data base are badly needed.
对1970年至1984年间发表的80篇论文进行了评估,以获取与化学物质诱导哺乳动物雄性生殖细胞非整倍体相关的结果。这些论文涵盖了多种检测方法和终点指标。被认为涉及直接测量非整倍体的检测方法基于减数分裂前、减数分裂和胚胎细胞以及雄性原核中的染色体计数,或者基于X连锁遗传标记的表型表达。那些将间接测量结果解释为非整倍体证据的检测方法主要包括评估交叉频率、单价体频率以及精子细胞/精子性染色体体计数的方法。初步筛选排除了数据不足以及未涉及单一化学测试剂的研究,从而使39篇论文不再接受进一步审查。其余41篇论文报告了46种不同化学物质的影响。对这些论文的实验方案是否充分、终点指标作为非整倍体直接测量的相关性以及数据呈现和统计分析的完整性进行了严格评估。还考虑了每种检测方法特有的标准。有4种化学测试被认为提供了可靠的非整倍体阳性或阴性数据。环磷酰胺和水合氯醛注入小鼠后均导致中期II超倍体。对三烯丙胺和异烟肼的分析非常有限,结果为阴性。44种化学物质的测试结果被认为不确定。得出的结论是,迫切需要对评估化学物质诱导雄性生殖细胞非整倍体的测试进行标准化,并应用这些测试来增加数据库。