Hansmann I, Probeck H D
Environ Health Perspect. 1979 Aug;31:161-5. doi: 10.1289/ehp.7931161.
Methods have been developed in the past to assess spontaneous and induced chromosomal aneuploidy in germ cells and in early pre- and postimplantation mammalian embryos. Some of these methods yield still more information when combined with chromosome banding techniques. Various chemicals and x-rays have been tested in mammalian oogenesis and x-rays in spermatogenesis. The inference may be drawn from these studies that spontaneous nondisjunction is considered to occur only rarely in mouse and hamster oogenesis and spermatogenesis. X-rays induce nondisjunction during male and femlae meiosis, thus giving rise to significantly more aneuploid oocytes and F1 embryos. The alkylating agents trenimone and cyclophosphamide induce chromosomal missegregation in oocytes; the incidence depends on the dose injected. Hormones used as oral contraceptives did cause aneuploidy in oocytes, but only after daily treatment with high doses. Hormones used for stimulated ovulation did not interfere with chromosome segregation in the mouse and Chinese and Syrian hamsters. The following problems may be considered in futre studies: the problem of a species-specificity for induced nondisjunction; the question of a stage sensitivity (transplacental treatment); what happens after chronic exposure, also at low doses; the presence of a threshold; the existence of a dose-effect relation; the nature of cellular target(s) responsible for induced nondisjunction (spindle, regulatory proteins for polymerization of microtubules and ther depolymerization, centrioles, centromeres, RNA, or gene expression); whether DNA is involved and whether repair capacity plays a role.
过去已经开发出多种方法来评估生殖细胞以及哺乳动物植入前和植入后早期胚胎中的自发和诱导染色体非整倍性。其中一些方法与染色体显带技术结合使用时能提供更多信息。已在哺乳动物卵子发生过程中测试了各种化学物质和X射线,并在精子发生过程中测试了X射线。从这些研究中可以推断,在小鼠和仓鼠的卵子发生和精子发生过程中,自发不分离被认为很少发生。X射线在雄性和雌性减数分裂过程中诱导不分离,从而产生明显更多的非整倍体卵母细胞和F1胚胎。烷基化剂曲尼莫酮和环磷酰胺在卵母细胞中诱导染色体错分;发生率取决于注射剂量。用作口服避孕药的激素确实会导致卵母细胞非整倍体,但只有在高剂量每日治疗后才会出现。用于促排卵的激素在小鼠、中国仓鼠和叙利亚仓鼠中不会干扰染色体分离。在未来的研究中可能会考虑以下问题:诱导不分离的物种特异性问题;阶段敏感性问题(经胎盘治疗);长期低剂量暴露后会发生什么;阈值的存在;剂量效应关系的存在;导致诱导不分离的细胞靶点的性质(纺锤体、微管聚合和解聚的调节蛋白、中心粒、着丝粒、RNA或基因表达);DNA是否参与以及修复能力是否起作用。