Mailhes J B, Yuan Z P, Aardema M J
Department of Obstetrics and Gynecology, Louisiana State University Medical Center, Shreveport 71130.
Mutat Res. 1990 Oct;242(2):89-100. doi: 10.1016/0165-1218(90)90034-y.
Assays are needed for detecting chemically-induced aneuploidy, for investigating the mechanisms of aneuploidy production, and for obtaining heritable germ cell data that can be used to formulate human risk estimates. In this report, we describe the results of experiments designed to study aneuploidy in metaphase II (MII) oocytes induced by intraperitoneal (i.p.) or oral dosages of colchicine, and to investigate the proportion of aneuploid oocytes transmitted to one-cell (1C) zygotes following oral administration of colchicine immediately following HCG. The proportions (and percentages) of hyperploid MII oocytes were: 1/606 (0.2), 37/504 (7.3), 152/731 (20.8) and 75/319 (23.5) for control, 0.2, 0.3 and 0.4 mg/kg, respectively for i.p. administration of colchicine; and 3/216 (1.4), 8/539 (1.5), 81/511 (15.9), 71/398 (17.8) and 98/391 (25.1) for control, 1.0, 2.0, 3.0 and 4.0 mg/kg, respectively for oral administration of colchicine. The proportions of hyperploid 1C zygotes were 2/327 (0.6), 21/389 (5.4), 62/435 (14.3) and 69/438 (15.8) for control, 2.0, 3.0 and 4.0 mg/kg, respectively for oral colchicine. The proportions of hyperploid MII oocytes and 1C zygotes were significantly higher (Chi-square, P less than 0.01) at each i.p. or oral dose (except 1.0 mg/kg oral) than in the controls. The frequencies of hyperploidy induced by oral doses of colchicine were greater in MII oocytes than in 1C zygotes. We also found that the frequency of developmentally delayed and polyploid 1C zygotes increased with the dose of oral colchicine. Developmentally delayed zygotes contained male-derived chromosomes and female-derived fragmented pronuclei and pronuclei with decondensed chromosomes. These results indicate that higher doses of oral colchicine are needed to induce comparable levels of aneuploidy found after i.p. administration, and that aneuploid oocytes are fertilized and reach first cleavage metaphase. In addition, colchicine induces a spectrum of events including aneuploidy, polyploidy and developmentally delayed oocytes and zygotes.
需要有检测化学物质诱导非整倍体的方法，用于研究非整倍体产生的机制，并获取可用于制定人类风险评估的可遗传生殖细胞数据。在本报告中，我们描述了旨在研究腹腔注射（i.p.）或口服秋水仙碱剂量诱导的中期 II（MII）卵母细胞中的非整倍体，以及研究在注射人绒毛膜促性腺激素（HCG）后立即口服秋水仙碱后，非整倍体卵母细胞传递到单细胞（1C）合子中的比例的实验结果。超倍体 MII 卵母细胞的比例（及百分比）分别为：对照组为 1/606（0.2%），腹腔注射秋水仙碱 0.2、0.3 和 0.4 mg/kg 组分别为 37/504（7.3%）、152/731（20.8%）和 75/319（23.5%）；口服秋水仙碱对照组为 3/216（1.4%），1.0、2.0、3.0 和 4.0 mg/kg 组分别为 8/539（1.5%）、81/511（15.9%）、71/398（17.8%）和 98/391（25.1%）。超倍体 1C 合子的比例分别为：对照组为 2/327（0.6%），口服秋水仙碱 2.0、3.0 和 4.0 mg/kg 组分别为 21/389（5.4%）、62/435（14.3%）和 69/438（15.8%）。在每个腹腔注射或口服剂量（口服 1.0 mg/kg 除外）下，超倍体 MII 卵母细胞和 1C 合子的比例均显著高于对照组（卡方检验，P 小于 0.01）。口服秋水仙碱剂量诱导的超倍体频率在 MII 卵母细胞中比在 1C 合子中更高。我们还发现，发育延迟和多倍体 1C 合子的频率随口服秋水仙碱剂量的增加而增加。发育延迟的合子包含雄性来源的染色体和雌性来源的碎片化原核以及染色体解聚的原核。这些结果表明，需要更高剂量的口服秋水仙碱才能诱导出与腹腔注射后相当水平的非整倍体，并且非整倍体卵母细胞能够受精并进入第一次卵裂中期。此外，秋水仙碱会诱导一系列事件，包括非整倍体、多倍体以及发育延迟的卵母细胞和合子。
