Fujii T
Teikyo University School of Medicine, Tokyo, Japan.
Cancer Causes Control. 1997 May;8(3):524-8. doi: 10.1023/a:1018477809755.
In order to prevent health risk from environmental chemicals, particularly for progeny, we have been performing a risk assessment for various chemicals including therapeutic agents. This paper reports the functional effects of maternal exposure to psychoactive drugs, anticancer drugs, or herbicides on the offspring of rats. Maternal exposure to imipramine in a dose equivalent to the therapeutic dose per unit body weight induced hyperthermic response to chlorpromazine in the male offspring, while normal control rats showed a marked hypothermia. Exposure to ethosuximide resulted in an increase in play fighting behavior in young offspring that was fostered by lactating normal mothers. Single exposures to nimustine or cisplatin, anticancer drugs, at a different gestational stage resulted in an acceleration of growth when exposed at the earlier stage of gestation. Moreover, cisplatin-exposed rats were emotionally unstable, showing a short latent time to the first line-crossing in an open-field during infantile period. The rats exposed to glufosinate ammonium, an herbicide, during the time of neurogenesis in the hippocampus showed a decrease in the wet-dog shakes response to kainic acid at six weeks of age. These results suggest that maternal exposure to chemicals during pregnancy induces a variety of functional abnormalities in the brain of the offspring dependent on the pharmacologic action of chemicals and the stage of gestation even with a single exposure.
为了预防环境化学物质带来的健康风险，尤其是对后代的影响，我们一直在对包括治疗药物在内的各种化学物质进行风险评估。本文报告了母体接触精神活性药物、抗癌药物或除草剂对大鼠后代的功能影响。母体以相当于每单位体重治疗剂量的剂量接触丙咪嗪，导致雄性后代对氯丙嗪产生体温过高反应，而正常对照大鼠则表现出明显的体温过低。接触乙琥胺导致幼崽玩耍打斗行为增加，这些幼崽由正常哺乳的母亲抚养。在不同的妊娠期单次接触抗癌药物尼莫司汀或顺铂，在妊娠早期接触会导致生长加速。此外，接触顺铂的大鼠情绪不稳定，在幼年期的旷场实验中首次穿越直线的潜伏时间较短。在海马体神经发生期接触除草剂草铵膦的大鼠，在6周龄时对 kainic 酸的湿狗摇反应减少。这些结果表明，即使单次接触，孕期母体接触化学物质也会根据化学物质的药理作用和妊娠期阶段，在后代大脑中诱发各种功能异常。
