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..

我们改进了体外神经毒理学试验系统，以评估这些化学品的神经毒性潜力。(1)本实验采用我们建立的神经细胞系N18 D2进行微核和微核率的测定。顺铂的凋亡诱导浓度比微核浓度高10倍。顺铂诱导的细胞凋亡在染毒后8 h达到高峰，染毒后24 h细胞微核率增加。另一方面，尼古丁本身诱导N18 D2细胞凋亡，但不诱导任何微核。细胞凋亡和微核的诱导可能成为化学物质神经毒性的标志。(2)细胞膜动作电位的变化DiBAC 4染色后用荧光光度计测定细胞膜动作电位。N18 DRG-D2的荧光强度在尼古丁暴露后增加，而在乙醇、甲醇、多聚甲醛、亚砷酸钠、二氯甲烷、二氯乙烷或二甲基亚砜暴露后降低。

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。

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。

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。

Yuji Suzuki: "Induction of micronuclei in mice exposed to static magnetic fields"Mutagenesis. 16-6. 499-501 (2001)

Yuji Suzuki：“暴露于静磁场的小鼠中微核的诱导”诱变。