A new method for evaluation of neurotoxicological chemicals

神经毒理学化学物质评价的新方法

• 批准号: 13670344
• 负责人: SUZUKI Yuji
• 金额: $ 2.56万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670344/
• 关键词: neurotoxicity; micronuclei; apoptosis; action potential; nicotine; ethanol; sodium arsenite; dichloroethane; 膜電位; ジクロロメタン; パラフォルムアルデヒド; 神経細胞; アルコール; 砒素; 電磁場; シスプラチン; エチルニトロソウレア

We improved a in vitro neurotoxicological test system for the purpose of assessing the neurotoxic potential of these chemicals.(1) Induction of micronuclei and apoptosisNeural cell line N18D2 which we established was used in this study. The apoptosis inducible concentration of cisplatin was ten-times higher than that of micronucleus. Induction of apoptosis was peaked at 8 h after exposure to cisplatin and frequency of micronuclei induced by cisplatin increased after 24 h after exposure. On the other hand, nicotine itself induced apoptosis in N18D2 cells but didn't induce any micronuclei. Both induction of apoptosis and micronuclei may become a maker of neurotoxisity of chemicals.(2) Alteration of membrane action potentialMembrane action potential was determined using a fluorophotometer after stained with DiBAC4. Fluorescence intensity of N18DRG-D2 was increased after exposure to nicotine but decreased after exposure to ethanol, methanol, paraformaldehyde, sodium arsenite, dichloromethane, dichloroethane or dimethylsulfoxide..

我们改善了一种体外神经毒理学测试系统，目的是评估这些化学物质的神经毒性潜力。（1）在本研究中使用了我们确定的微核和凋亡静脉内细胞系N18D2的诱导。顺铂的凋亡诱导浓度比微核的凋亡浓度高十倍。暴露于顺铂后8小时，凋亡的诱导峰值，在暴露后24小时后，由顺铂诱导的微核中的频率增加。另一方面，尼古丁本身会诱导N18D2细胞的凋亡，但没有诱导任何微核。凋亡的诱导和微核的诱导均可成为化学物质神经毒性的制造商。（2）使用DIBAC4染色后，使用荧光计测定膜作​​用电位的势能动作电位。暴露于尼古丁后，N18DRG-D2的荧光强度增加，但在暴露于乙醇，甲醇，多聚甲醛，砷酸钠，二氯甲烷，二氯甲烷或二甲基磺酰氧化物中后，荧光强度降低了。

项目成果

Yuji Suzuki: "Induction of micronuclei in FLC-4 human hepatocellular cell by mutagenic agents"Environmental Sciences. 9. 309-318 (2002)

Yuji Suzuki：“诱变剂诱导 FLC-4 人肝细胞中的微核”环境科学。

Yuji Suzuki: "Induction of micronuclei in mice exposed to static magnetic fields"Mutagenesis. 16. 499-501 (2001)

Yuji Suzuki：“暴露于静磁场的小鼠中微核的诱导”诱变。

Yuji Suzuki: "Induction of micronuclei in FLC-4 human hepatocellular carcinoma cell by mutagenic agents"Environmental Sciences. 9-4. 309-318 (2002)

Yuji Suzuki：“通过诱变剂诱导 FLC-4 人肝细胞癌细胞中的微核”环境科学。

Atsushi Nagai: "Generation and characterization of human hybrid neurons produced between embryonic CNS neurons and neuroblastoma cells"Neurobiology of disease. 11. 184-198 (2002)

Atsushi Nagai：“胚胎中枢神经系统神经元和神经母细胞瘤细胞之间产生的人类混合神经元的生成和表征”疾病的神经生物学。

Akira Takahashi: "Genotoxic effect of nitrosamine compounds in a human liver cell line (FLC-4)"Jikeikai Medical Journal. 49-4. 143-148 (2002)

Akira Takahashi：“亚硝胺化合物对人肝细胞系（FLC-4）的基因毒性作用”Jikeikai 医学杂志。