Development of the evaluative method for harmful effects of environmental pollutant on the neurotransmission and genetic transcription.

本研究旨在建立一种评价环境污染物对神经传递和基因转录的影响的方法。主要研究结果如下：1.为阐明内分泌干扰物对生物体的影响，以PC 12细胞为材料，研究了低浓度三丁基锡（TBT）和2，4，5-三氯苯氧乙酸（2，4，5-T）对细胞凋亡和分化的影响。TBT或2，4，5-T可抑制培养细胞的凋亡和分化。自然发生的神经元死亡是脊椎动物神经系统发育过程中发生的公认现象。研究结果表明，三丁基锡化合物或2，4，5-睾酮等化学物质有可能阻止哺乳动物体内的细胞分化和/或发育。由于细胞凋亡和细胞分化对于正常发育和消除有害细胞至关重要，因此TBT和2，4，5-T抑制细胞凋亡和分化将对个体造成损害。采用电记录和光记录方法研究了三氯乙烯（TCE）对LTP的影响。TCE组的群体峰电位（PS）的前后比小于对照组。光信号的后/前比值在TCE中小于对照。提示LTP损伤可能是TCE急性暴露后即刻记忆损伤的机制之一。

In the present study, we intended to develop the evaluative method for harmful effects of environmental pollutant on the neurotransmission and genetic transcription. Main results obtained in the present investigations are as follows;1.To elucidate the effects of the endocrine disrupters on bioorganisms, the influence of Tributyltin (TBT) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) on apoptosis and differentiation at low concentrations using PC12 cell were investigated. TBT or 2,4,5-T suppressed the apoptosis and differentiation of the cultured cells. Naturally occurring neuronal death is a well-established phenomenon that occurs during development of the vertebrate nervous system. The results of the study indicated the possibility that the chemical substances such as TBT or 2,4,5-T could prevent cell differentiation and/or development in the mammalian body. Since apoptosis and cell differentiation are essential for normal development and elimination of harmful cells, suppression of apoptosis and differentiation by TBT and 2,4,5-T would be damaging for individuals.2. The effect of trichloroethylene (TCE) on LTP was studied using both electrical and optical recording. The post per pre ratio of population spikes (PS) was smaller in TCE groups than in the control. The post per pre ratio of the optical signals was smaller in TCE than in the control. It was suggested that the impairment of LTP may be one of the mechanisms of the impairment of the immediate memory after the acute exposure to TCE in human.