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

1.比较了1-溴丙烷对两个近交系大鼠品系WNA（Wistar名古屋）和F344的神经元效应，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株菌基因表达的差异。结果表明，F344比WNA更易受到神经元效应的影响。基因芯片研究表明，谷胱甘肽S-转移酶和环氧水解酶的表达通过两个菌株增强。神经元再生相关基因在WNA中表达增强，而在F344中表达受到抑制，表现出对两个菌株的相反作用。该基因与两株易感性差异的关系尚需进一步研究.采用GC-MS和LC-MS/MS检测大鼠吸入实验所得尿液中的代谢产物N-乙酰基S-丙基半胱氨酸。该方法也成功地应用于人体样品.蛋白加合物S-丙基半胱氨酸检测与LC-MS/MS从大鼠接触1-溴丙烷获得的珠蛋白。该方法已成功应用于人体样品.谷胱甘肽S-转移酶多态性的研究阐明了接触1-溴丙烷工人谷胱甘肽S-转移酶的剂量反应关系。

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.