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

1. 比较了两种自交系大鼠WNA （Wistar Nagoya）和F344对1-溴丙烷暴露的神经效应，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菌株基因表达差异。结果表明，F344比WNA更易受神经元效应的影响。微阵列研究表明，两株菌株的谷胱甘肽s -转移酶和环氧水解酶的表达均增强。神经元再生相关基因在WNA中表达增强，而在F344中表达抑制，在两种菌株中表现出对比效应。该基因与两种菌株的易感性差异之间的关系有待进一步研究。采用气相色谱-质谱联用和液相色谱-质谱联用检测大鼠吸入实验尿液中代谢物n -乙酰s -丙基半胱氨酸。该方法也成功地应用于人体样本。用LC-MS/MS检测1-溴丙烷暴露大鼠球蛋白中的蛋白质加合物s -丙基半胱氨酸。该方法已成功地应用于人体样本。谷胱甘肽s -转移酶多态性的研究阐明了1-溴丙烷暴露工人的剂量反应关系。

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.