Abstract
The aim of this study was to clarify whether phenotypic variation exists when subjects with different genotypes of cytochrome P450 2E1 (CYP2E1) are exposed to N,N-dimethylformamide (DMF). The genotypes of CYP2E1 were confirmed in 123 healthy male volunteer subjects. Of the 123 subjects, the numbers of c1 homozygotes, c2 heterozygotes, and c2 homozygotes were 77, 45, and 1, respectively. Seven of the c1 homozygotes, five of the c2 heterozygotes, and the one c2 homozygote (mean age: 22.7 years, range: 20-27 years) were exposed to DMF vapor twice, once via the skin and once via the lung, for a total of 8 h per subject at a concentration below 10 ppm, the occupational exposure limit recommended by the Japan Society for Occupational Health, the American Conference of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft, at 27°C and 44% relative humidity. Exposure levels were 6.2 ± 1.0 ppm in dermal exposure and 7.1 ± 1.0 ppm in inhalation exposure. Urine samples were collected until 72 h after exposure. The half-lives of urinary N-methylformamide (NMF) were obtained as the phenotype. The average urinary NMF half-lives of the c1 homozygotes, the c2 heterozygotes, and the c2 homozygote were 3.86 ± 1.90, 4.38 ± 1.53, and 4.2 h after dermal exposure, and 1.58 ± 0.42, 1.84 ± 0.61, and 3.2 h after respiratory exposure. The NMF half-lives of the c1 homozygotes were not significantly different from those of the c2 heterozygotes, and there were no differences between the NMF half-lives on the subjects with and without the c2 allele. Even though the data were obtained from only one c2 homozygote, it is noteworthy that the NMF half-life of this subject was slightly less than that of the c1 homozygotes after respiratory exposure.
| Original language | English |
|---|---|
| Pages (from-to) | 755-759 |
| Number of pages | 5 |
| Journal | Archives of Toxicology |
| Volume | 74 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2001 |
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Keywords
- Cytochrome
- Genetic polymorphism
- Genotype
- N,N-Dimethylformamide
- P450 2E1
- Phenotype
ASJC Scopus subject areas
- Toxicology
- Health, Toxicology and Mutagenesis
Cite this
Does the polymorphism of cytochrome P-450 2E1 affect the metabolism of N,N-dimethylformamide? Comparison of the half-lives of urinary N-methylformamide. / Nomiyama, Tetsuo; Nakashima, Hiroshi; Sano, Yuri; Chen, Li Ling; Tanaka, Shigeru; Miyauchi, Hiroyuki; Yamauchi, Tsuneyuki; Sakurai, Haruhiko; Omae, Kazuyuki.
In: Archives of Toxicology, Vol. 74, No. 12, 2001, p. 755-759.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Does the polymorphism of cytochrome P-450 2E1 affect the metabolism of N,N-dimethylformamide? Comparison of the half-lives of urinary N-methylformamide
AU - Nomiyama, Tetsuo
AU - Nakashima, Hiroshi
AU - Sano, Yuri
AU - Chen, Li Ling
AU - Tanaka, Shigeru
AU - Miyauchi, Hiroyuki
AU - Yamauchi, Tsuneyuki
AU - Sakurai, Haruhiko
AU - Omae, Kazuyuki
PY - 2001
Y1 - 2001
N2 - The aim of this study was to clarify whether phenotypic variation exists when subjects with different genotypes of cytochrome P450 2E1 (CYP2E1) are exposed to N,N-dimethylformamide (DMF). The genotypes of CYP2E1 were confirmed in 123 healthy male volunteer subjects. Of the 123 subjects, the numbers of c1 homozygotes, c2 heterozygotes, and c2 homozygotes were 77, 45, and 1, respectively. Seven of the c1 homozygotes, five of the c2 heterozygotes, and the one c2 homozygote (mean age: 22.7 years, range: 20-27 years) were exposed to DMF vapor twice, once via the skin and once via the lung, for a total of 8 h per subject at a concentration below 10 ppm, the occupational exposure limit recommended by the Japan Society for Occupational Health, the American Conference of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft, at 27°C and 44% relative humidity. Exposure levels were 6.2 ± 1.0 ppm in dermal exposure and 7.1 ± 1.0 ppm in inhalation exposure. Urine samples were collected until 72 h after exposure. The half-lives of urinary N-methylformamide (NMF) were obtained as the phenotype. The average urinary NMF half-lives of the c1 homozygotes, the c2 heterozygotes, and the c2 homozygote were 3.86 ± 1.90, 4.38 ± 1.53, and 4.2 h after dermal exposure, and 1.58 ± 0.42, 1.84 ± 0.61, and 3.2 h after respiratory exposure. The NMF half-lives of the c1 homozygotes were not significantly different from those of the c2 heterozygotes, and there were no differences between the NMF half-lives on the subjects with and without the c2 allele. Even though the data were obtained from only one c2 homozygote, it is noteworthy that the NMF half-life of this subject was slightly less than that of the c1 homozygotes after respiratory exposure.
AB - The aim of this study was to clarify whether phenotypic variation exists when subjects with different genotypes of cytochrome P450 2E1 (CYP2E1) are exposed to N,N-dimethylformamide (DMF). The genotypes of CYP2E1 were confirmed in 123 healthy male volunteer subjects. Of the 123 subjects, the numbers of c1 homozygotes, c2 heterozygotes, and c2 homozygotes were 77, 45, and 1, respectively. Seven of the c1 homozygotes, five of the c2 heterozygotes, and the one c2 homozygote (mean age: 22.7 years, range: 20-27 years) were exposed to DMF vapor twice, once via the skin and once via the lung, for a total of 8 h per subject at a concentration below 10 ppm, the occupational exposure limit recommended by the Japan Society for Occupational Health, the American Conference of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft, at 27°C and 44% relative humidity. Exposure levels were 6.2 ± 1.0 ppm in dermal exposure and 7.1 ± 1.0 ppm in inhalation exposure. Urine samples were collected until 72 h after exposure. The half-lives of urinary N-methylformamide (NMF) were obtained as the phenotype. The average urinary NMF half-lives of the c1 homozygotes, the c2 heterozygotes, and the c2 homozygote were 3.86 ± 1.90, 4.38 ± 1.53, and 4.2 h after dermal exposure, and 1.58 ± 0.42, 1.84 ± 0.61, and 3.2 h after respiratory exposure. The NMF half-lives of the c1 homozygotes were not significantly different from those of the c2 heterozygotes, and there were no differences between the NMF half-lives on the subjects with and without the c2 allele. Even though the data were obtained from only one c2 homozygote, it is noteworthy that the NMF half-life of this subject was slightly less than that of the c1 homozygotes after respiratory exposure.
KW - Cytochrome
KW - Genetic polymorphism
KW - Genotype
KW - N,N-Dimethylformamide
KW - P450 2E1
KW - Phenotype
UR - http://www.scopus.com/inward/record.url?scp=0034467648&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034467648&partnerID=8YFLogxK
U2 - 10.1007/s002040000197
DO - 10.1007/s002040000197
M3 - Article
VL - 74
SP - 755
EP - 759
JO - Archiv fur Toxikologie
JF - Archiv fur Toxikologie
SN - 0003-9446
IS - 12
ER -