Köpf-Maier P, Brauchle U, Heussler A
Institut für Anatomie, Freie Universität Berlin, F.R.G.
Toxicology. 1988 Mar;48(3):253-60. doi: 10.1016/0300-483x(88)90106-0.
The passage of titanium-containing metabolites across the placenta into the embryonal compartment was investigated by analyzing the titanium (Ti) content in embryos/fetuses at various intervals between 1 h and 24 h after treatment of pregnant mice with single doses of the antitumor agent titanocene dichloride (C5H5)2TiCl2 (60 mg/kg) on days 10, 12, 14 or 16 of gestation. The Ti concentration was determined using flameless atomic absorption spectroscopy. After treatment on days 10, 12 or 14, the Ti concentrations were not elevated in comparison to untreated embryos. Only on day 16, i.e. beyond the end of organogenesis, small amounts of Ti were detectable in the fetal compartment 4-24 h after substance application, exceeding the control values by factors ranging between 2 and 3. These results explain the absence of histologic lesions in developing embryonal organs and the lack of multiple teratogenic effects in new-borns after application of therapeutic doses of (C5H5)2TiCl2 to pregnant mice during the embryonal organogenesis.
通过分析妊娠第10、12、14或16天用单剂量抗肿瘤剂二氯二茂钛（C5H5）2TiCl2（60mg/kg）处理的怀孕小鼠后，在1小时至24小时的不同时间间隔内胚胎/胎儿中的钛（Ti）含量，研究了含钛代谢物穿过胎盘进入胚胎区室的情况。使用无火焰原子吸收光谱法测定钛浓度。在第10、12或14天处理后，与未处理的胚胎相比，钛浓度没有升高。仅在第16天，即在器官发生结束后，在给药后4-24小时在胎儿区室中可检测到少量钛，超过对照值2至3倍。这些结果解释了在胚胎器官发生期间给怀孕小鼠施用治疗剂量的（C5H5）2TiCl2后，发育中的胚胎器官中没有组织学损伤以及新生儿中没有多种致畸作用的原因。
