Mahalik M P, Hitner H W, Prozialeck W C
Department of Pharmacology, Lake Erie College of Osteopathic Medicine, PA 16509, USA.
Toxicol Lett. 1995 Apr;76(3):195-202. doi: 10.1016/0378-4274(95)80003-v.
Studies to identify the mechanisms underlying the teratogenic effects of cadmium (Cd2+) have been complicated by the inherent difficulties of chronically and subchronically administering specific doses of Cd2+ to gravid animals under strictly controlled conditions. The objective of the present study was to develop a relatively simple animal model for examining the teratogenic effects of subchronic Cd2+ exposure. Cd2+ was administered to gravid CF-1 mice by subcutaneously implanted Alzet osmotic minipumps, which released fixed amounts of Cd2+ over a 14-day period between days 5 and 18 of gestation. The results showed that Cd2+ administered in this manner produced fetal anomalies and that the patterns of Cd2+ distribution and the specific developmental defects were similar to those that have been reported for other routes of Cd2+ administration. These findings indicate that osmotic minipumps may serve as useful tools in long-term studies of Cd2+ teratogenicity. They would appear to be especially useful in teratogenic evaluations where minimizing maternal stress and administering precise doses of Cd2+ are important.
确定镉(Cd2+)致畸作用潜在机制的研究因在严格控制条件下对妊娠动物长期和亚慢性给予特定剂量的Cd2+存在固有困难而变得复杂。本研究的目的是建立一个相对简单的动物模型,用于研究亚慢性Cd2+暴露的致畸作用。通过皮下植入Alzet渗透微型泵向妊娠CF-1小鼠给予Cd2+,该微型泵在妊娠第5天至18天的14天内释放固定量的Cd2+。结果表明,以这种方式给予的Cd2+会导致胎儿畸形,并且Cd2+的分布模式和特定的发育缺陷与其他Cd2+给药途径所报道的相似。这些发现表明,渗透微型泵可作为Cd2+致畸性长期研究的有用工具。它们在致畸评估中似乎特别有用,在这些评估中,尽量减少母体应激和给予精确剂量的Cd2+很重要。