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

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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.