Tanaka H, Inomata K, Arima M
Division of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, NCNP, Tokyo, Japan.
J Nutr Sci Vitaminol (Tokyo). 1993 Apr;39(2):177-88. doi: 10.3177/jnsv.39.177.
The teratogenic effects of triethylene tetramine dihydrochloride (Trien-2HCl) on fetal mouse brain were studied on gestational day 19. Trien-2HCl was given throughout pregnancy at levels of 0 (control), 3,000, 6,000, or 12,000 mg/liter as drinking water, ad libitum. Mean litter size and live fetus per dam at birth were not significantly different among the four groups. The frequency of gross brain abnormalities in live fetus at birth such as hemorrhages, delayed ossification in cranium, hydrocephaly, exencephaly, and microcephaly increased with increasing levels of the drug. Microscopically, disorganization of neuronal cell layers, spongiform changes in white matter, and reduced myelin development were noted in the coronally sectioned cerebrum from Trien-2HCl-treated fetus. These abnormal findings increased dose-dependently in regard to the extent and severity at the levels of 6,000 and 12,000 mg/liter. No such changes were observed in the cerebrum of controls. These results suggest that microscopic changes in fetal brain caused by Trien-2HCl may be in part similar to those in brindled mutant mouse. Special attention should be paid to the developing fetal brain when Trien-2HCl is used during pregnancy.
在妊娠第19天研究了二盐酸三乙烯四胺（Trien-2HCl）对胎鼠脑的致畸作用。在整个孕期，随意饮用含0（对照）、3000、6000或12000mg/L的Trien-2HCl的饮用水。四组之间出生时平均窝仔数和每只母鼠的活胎数无显著差异。出生时活胎中严重脑异常（如出血、颅骨骨化延迟、脑积水、无脑畸形和小头畸形）的发生率随药物剂量增加而升高。显微镜下，在Trien-2HCl处理的胎鼠冠状切面上，大脑神经元细胞层紊乱、白质海绵状改变以及髓鞘发育减少。在6000和12000mg/L剂量水平，这些异常发现的程度和严重程度呈剂量依赖性增加。对照组大脑未观察到此类变化。这些结果表明，Trien-2HCl引起的胎鼠脑微观变化可能部分类似于斑驳突变小鼠的变化。孕期使用Trien-2HCl时，应特别关注发育中的胎鼠脑。
