Zagon I S, McLaughlin P J
Brain Res Bull. 1981 May;6(5):355-60. doi: 10.1016/s0361-9230(81)80003-2.
Female rats were injected (IP) with either 15, 60, 100, or 150 mg/kg N-ethyl-N-nitrosourea (ENU) on gestation day 18. The neurochemical development of the whole brain and the cerebellum was studied in 21- and 60-day old offspring; pups from mothers subjected to 150 mg/kg were examined only at 21 days. Brain weights were significantly reduced in all ENU-exposed groups at 21 days, and the 60 mg/kg group at 60 days. Whole brain DNA and protein concentrations of most ENU groups were elevated at 21 days and RNA content and RNA/DNA ratios were subnormal. Deficits in whole brain DNA content were observed in all ENU groups on day 60. Cerebellar weight was reduced in the 60 and 150 mg/kg groups on day 21 and in the 100 mg/Kg group on day 60. At 21 days, reductions in cerebellar DNA and RNA concentrations and contents were often recorded in several ENU groups. Cerebellar DNA concentration and content of the 60 and 100 mg/kg groups remained subnormal at 60 days of age. In general, a dose-response effect was evident in the number and magnitude of neurochemical alterations produced by ENU. These data suggest that transplacental exposure to ENU, a potent neurotropic carcinogen, affects the biochemical maturation of the brain.
在妊娠第18天，给雌性大鼠腹腔注射15、60、100或150mg/kg的N-乙基-N-亚硝基脲（ENU）。对21日龄和60日龄后代的全脑和小脑的神经化学发育进行了研究；仅对接受150mg/kg剂量的母鼠所产幼崽在21日龄时进行了检查。在21日龄时，所有ENU暴露组的脑重量均显著降低，60日龄时60mg/kg组的脑重量也显著降低。大多数ENU组在21日龄时全脑DNA和蛋白质浓度升高，RNA含量和RNA/DNA比值低于正常水平。在60日龄时，所有ENU组均观察到全脑DNA含量不足。21日龄时，60mg/kg和150mg/kg组的小脑重量降低，60日龄时100mg/kg组的小脑重量降低。在21日龄时，几个ENU组经常记录到小脑DNA和RNA浓度及含量的降低。60mg/kg和100mg/kg组在60日龄时小脑DNA浓度和含量仍低于正常水平。一般来说，ENU产生的神经化学改变的数量和程度存在明显的剂量反应效应。这些数据表明，经胎盘暴露于强效嗜神经致癌物ENU会影响大脑的生化成熟。
