Samarawickrama G P, Webb M
Environ Health Perspect. 1979 Feb;28:245-9. doi: 10.1289/ehp.7928245.
In rats, of the Wistar-Porton strain, a single intravenous injection of 1.25 mg Cd2+ between days 9 and 15 of gestation results in a high incidence (80% of hydrocephalus, together with other malformations in the fetuses, examined on day 20. This dose is critical, since 1.1 mg Cd2+/kg is not teratogenic, while 1.35 mg Cd2+/kg kills all the embryos. Intravenous injection of Cd2+ to the pregnant rat on day 12 causes a dose-dependent inhibition of placental Zn2+ transport. At the teratogenic dose, Zn2+ transport is inhibited by about 75% at 4 hr. Thereafter, inhibition decreases with time but is still significant at 48 hr. At 20 hr after administration of Cd2+ the embryonic concentration of Zn2+ is depressed by 33%. In the whole embryo the activity of the Zn2+-dependent thymidine kinase is inhibited by about 60% at 4 hr and at 20 hr the DNA concentration is reduced significantly. Placental transport of 14C-leucine and 14C-uridine, as well as the embryonic incorporation of these precursors into protein and RNA is unaffected at least at short times after the administration of Cd2+. It is possible therefore, that the teratogenic effects of Cd2+ may be related to the inhibition of DNA synthesis in the embryo.
在Wistar-Porton品系的大鼠中,在妊娠第9至15天单次静脉注射1.25毫克Cd2+会导致高发生率(80%)的脑积水,以及胎儿的其他畸形,在第20天进行检查。这个剂量很关键,因为1.1毫克Cd2+/千克没有致畸性,而1.35毫克Cd2+/千克会杀死所有胚胎。在第12天给怀孕大鼠静脉注射Cd2+会导致胎盘Zn2+转运的剂量依赖性抑制。在致畸剂量下,4小时时Zn2+转运被抑制约75%。此后,抑制作用随时间降低,但在48小时时仍很显著。在给予Cd2+ 20小时后,胚胎中Zn2+的浓度降低了33%。在整个胚胎中,依赖Zn2+的胸苷激酶的活性在4小时时被抑制约60%,在20小时时DNA浓度显著降低。至少在给予Cd2+后的短时间内,14C-亮氨酸和14C-尿苷的胎盘转运以及这些前体在胚胎中掺入蛋白质和RNA的过程不受影响。因此,Cd2+的致畸作用可能与胚胎中DNA合成的抑制有关。