Investigation on protein adduct produced by alternatives to ozone-depleting substances and susceptibility genes and establishment of new method for risk assessment.

消耗臭氧层物质替代品与易感基因产生的蛋白质加合物的调查及风险评估新方法的建立。

• 批准号: 16390169
• 负责人: ICHIHARA Gaku
• 金额: $ 9.6万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390169/
• 关键词: 1-bromopropane; protein adduct; susceptibility gene; dose-response relationship; neurotoxicity; microarray; mass spectrometry; risk assessment; フロン代替物質; 感受性; 曝露指標; 遺伝子発現; GST; LC-MS; グロビン蛋白; F344; Wistar

1. The neuronal effects of 1-bromopropane in two inbred rat strains WNA (Wistar Nagoya) and F344 were compared to find genes related with susceptibility to 1-bromopropane exposure. Oligonucleotide microarray was applied to detect the difference of gene expression in two strains. The results showed that F344 is more susceptible than WNA in neuronal effects. The microarray study showed that glutathione S-transferase and epoxy hydrolase's expression were enhanced thorough two strains. Neuronal regeneration related gene was enhanced in WNA but suppressed in F344, showing a contrasting effect on two strains. Further investigation is needed to understand how this gene is related with the difference of susceptibility in two strains.2. Metabolite N-acetyl S-propyl cysteine was detected with GC-MS and LC-MS/MS in the urine obtained from inhalation experiments using rats. This method is also applied to human samples successfully.3. Protein adduct S-propyl cysteine was detected with LC-MS/MS in globin obtained from rats exposed to 1-bromopropane. This method is applied to human samples successfully.4. Investigation on polymorphism of glutathione S-transferase clarify the dose responserelationship in the workers exposed to 1-bromopropane.

1.比较1-溴丙烷对两种近交系大鼠WNA（Wistar Nagoya）和F344的神经元影响，以寻找与1-溴丙烷暴露易感性相关的基因。应用寡核苷酸芯片检测两个菌株基因表达的差异。结果表明，F344 在神经元效应方面比 WNA 更敏感。微阵列研究表明，两种菌株的谷胱甘肽S-转移酶和环氧水解酶的表达均得到增强。神经元再生相关基因在 WNA 中增强，但在 F344 中受到抑制，在两种菌株中显示出对比效果。该基因与两个菌株的易感性差异有何关系，还需进一步研究。 2．使用 GC-MS 和 LC-MS/MS 在大鼠吸入实验获得的尿液中检测到代谢物 N-乙酰基 S-丙基半胱氨酸。该方法也成功应用于人体样本。 3．使用 LC-MS/MS 在从暴露于 1-溴丙烷的大鼠获得的珠蛋白中检测到蛋白质加合物 S-丙基半胱氨酸。该方法已成功应用于人体样本。 4．谷胱甘肽S-转移酶多态性研究阐明了1-溴丙烷作业工人的剂量反应关系。

项目成果

A survey on exposure level, health status, and biomarkers in workers exposed to 1-bromopropane

• DOI: 10.1002/ajim.10320
• 发表时间: 2004-01-01
• 期刊: AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
• 影响因子: 3.5
• 作者: Ichihara, G;Li, WH;Takeuchi, Y
• 通讯作者: Takeuchi, Y

Investigation of Toxicity through Human Cases and Animal Experiments-study of bromopropanes-

通过人体案例和动物实验研究毒性-溴丙烷的研究-

• 发表时间: 2005
• 期刊: Japanese Journal of Hygiene 60
• 作者: Ryozo Matsuda;Tokuko Munesue (eds.);Ichihara S. et al.;Ichihara S. et al.;Ito Y.et al.;Okamura A. et al.;Ichihara G. et al.
• 通讯作者: Ichihara G. et al.

A role for the aryl hydrocarbon receptor in regulation of ischemia-induced angiogenesis

• DOI: 10.1161/atvbaha.106.138701
• 发表时间: 2007-06-01
• 期刊: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
• 影响因子: 8.7
• 作者: Ichihara, Sahoko;Yamada, Yoshiji;Murohara, Toyoaki
• 通讯作者: Murohara, Toyoaki

A survey of semen indices in insecticide sprayers

• DOI: 10.1539/joh.46.109
• 发表时间: 2004-03-01
• 期刊: JOURNAL OF OCCUPATIONAL HEALTH
• 影响因子: 3
• 作者: Kamijima, M;Hibi, H;Takeuchi, Y
• 通讯作者: Takeuchi, Y

Pravastatin increases survival and suppresses an increase in myocardial matrix metalloproteinase activity in a rat model of heart failure

• DOI: 10.1016/j.cardiores.2005.08.001
• 发表时间: 2006-02-15
• 期刊: CARDIOVASCULAR RESEARCH
• 影响因子: 10.8
• 作者: Ichihara, S;Noda, A;Yokota, M
• 通讯作者: Yokota, M