|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1995 : ¥700,000 (Direct Cost : ¥700,000)
The effects of genetic polymorphisms of drug metabolizing enzymes, which are aldehyde dehydrogenase 2 (ALDH2) , cytochrome P-450s (CYP1A1, CYP2E1) , glutathione-S-transferase M1 (GSTM1) , N-acetyltransferase 2 (NAT2) and so on, on the metabolism and excretion of the environmental hazardous substances were studied in the various human populations. The exposure levels to the substances were estimated by a personal monitoring budge or a questionnaire, and their metabolites in urine were also measured using HPLC.
Urinary hippuric acid, a main metabolite of toluene, is significantly lower among the workers with the homozygous genotype of inactive ALDH2 than that in the workers with the homozygous genotype of normal ALDH2. There were no urinary specimens above 3.0 g/l of hippuric acid from the workers with homozygous genotype of inactive ALDH2. Urinary concentration of 1-pyrenol, which is one of the main metabolites of pyrene, is higher in smokers and in the subjects who eat more meat and fish. However, there is no statistical relation between urinary 1-pyrenol concentration and the genetic polymorphisms of the metabolizing enzymes. Urinary concentration of cotinine, which is a main metabolite of nicotine, is lower in the homozygote of wild CYP2E1 allele than the homozygote of mutant CYP2E1 allele and the heterozygote after correcting cigarette consumption. It suggests that CYP2E1 polymorphism affects the nicotine metabolism. Urinary caffeine concentration in smokers was significantly lower than that in nonsmoker when it is compared among the subjects who drink almost same amount of coffee or tea. It is suggested that smoking accelerate the caffeine metabolism.