| Project/Area Number |
12670392
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Mie University |
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Principal Investigator |
YAMAMOTO Hidetaka Mie University, Faculty of Medicine, Assistant, 医学部, 助手 (90158296)
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| Co-Investigator(Kenkyū-buntansha) |
TANEGASHIMA Akio Mie University, Faculty of Medicine, Lecturer, 医学部, 講師 (70283520)
FUKUNAGA Tatsushige Mie University, Faculty of Medicine, Professor, 医学部, 教授 (70156800)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Alcohol, ethyl / CYP2E1 / ALDH / Acetaldehyde / cDNA / mRNA / RT-PCR / Polymorphism / Alcohol,ethyl / Ethanol |
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| Research Abstract |
It is well established that cytochrome P450 isozymes are active in the metabolic conversion of many structurally diverse chemicals to electrophiles capable of reacting with cellular macromolecules. Thus, procarcinogens can be bioactivated to reactive species and can covalently modify chromosomal DNA causing irreversible cellular changes that may ultimately lead to cancer. The aim of this study was to estimate the extent of induced CYP2E1 level being focused on the organ damage by ethanol, and to elucidate the onset mechanism of organ damage on alcoholics. There were no differences between the healthy individuals without drinking and with habitual drinking in CYP2E1mRNA levels using Reverse Transcription-PCR (RT-PCR). Moreover, there were also no differences of the expressed levels of CYP2E1mRNAin each of the three genotypes of ALDH2 when various concentrations of ethanol were added in the blood and incubated at 37 ℃ for a definite time in vitro. It was suggested that the drinking frequ
… More
ency or the strength ofALDH2 activity has no effect on the expressed levels of CYP2E1mRNA.
And we investigated the ADH3 polymorphism in the Finnish population to reveal the role of ADH3 genotypes in the acute effects of alcohol. We analyzed the ADH3 genotypes from a control population and from a selected population chosen for unusual reactions to low alcohol intake. In addition to the ADH3 genotype determinations by PCR, alcohol drinking and flushing were assessed by self-estimation questionnaires. A rather equal distribution of the ADH3 alleles in both the control and selected groups were displayed. Flushing was more prevalent within the 1/1 males than the 2/2 males (both groups). A tendency to a similar association was seen in the women. In the men flushing tended to correlate positively with alcohol drinking, but in the women there was an opposite tendency. The ADH3^*1 allele was almost exclusively prevalent in the binge drinking men in the selected group, reporting unusual reactions to alcohol. Less
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