|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1999 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1998 : ¥2,600,000 (Direct Cost : ¥2,600,000)
Cytocrome P450 2E1 (CYP2E1) is enrolled to metabolism of chemical substances. Promoter region of CYP2E1 is polymorphic, namely genotype 1/1, 1/2 and 2/2. Expression level becomes higher in that order. In this study, we investigated relationship between CYP2E1 genotype and metabolism or health effect through the study of dimethylformamide (DMF), which is toxic to liver, absorbed through Skin.
Metabolism Eleven volunteers were exposed to DMF and the biological half-life (BHL) of n-monomthylformamide (NMF), which is the metabolite of DMF, was examined. Especially when DMF was absorbed through skin, BHL showed stepwise decrease (4.7±1.4 hours for 1/1 type (n=7), 3.9±0.5 hours for 1/2 type (n=3) and 3.1 hours for 2/2 type (n=1)). But, it was difficult to say conclusive thing for its small sample size. We exposed two new 1/2 type volunteers to DMF. Analysis including the result of two new volunteer is now under way.
Dimethylacetoamide (DMAc) is also metabolized by CYP2E1. Because we have the volunteer exposure experiment data of DMAc, we examined the genotype of volunteers. We failed to analize the relationship of CYP2E1 genotype and DMAc metabolism, because all of volunteers was 1/1 type.
Health effect Cross-sectional study was done in the factory where people handle with DMF. We planned to examine two things. 1) Is there any adverse health effect due toDMF? 2) Does genotype of CYP2E1 affect the result, if we observed adverse health effect? Attention was specially paid to hepatic or neuronal function (both central and peripheral nervous system). Some items on subjective symptom or objective examination such as clinical chemistry showed tentative positive result, but we could not observe positive relationship after adjustment of confounding factors. In the factory we studied, no clear-cut adverse health effect was observed. Therefore, no modification by CYP2E1