Relationship between the expression of cytochrome P450 2E1 in human lymphocyte and the organ damage

众所周知，细胞色素P450同工酶在许多结构不同的化学物质的代谢转化为能够与细胞大分子发生反应的亲电体的过程中发挥着积极的作用。因此，前致癌物可以被活性物质激活，并可以共价修饰染色体DNA，导致不可逆的细胞变化，最终可能导致癌症。本研究的目的是估计酒精所致器官损伤所致的细胞色素P450-2E_1水平的变化程度，并阐明酒精对器官损伤的发病机制。逆转录-聚合酶链式反应(RT-PCR)结果显示，不饮酒和习惯性饮酒的健康人之间的CYP2E1mRNA水平差异无统计学意义。此外，在血液中加入不同浓度的乙醇并在体外37℃孵育一定时间后，三种ALDH2型细胞色素P450 2E1mRNAs的表达水平也没有差异。有人建议饮酒的人…ALDH2活性的增加或强度对CYP2E1mRNA的表达水平没有影响。我们研究了芬兰人群中ADH3基因的多态性，以揭示ADH3基因在酒精急性效应中的作用。我们分析了来自对照人群和被选为对低酒精摄入有异常反应的人群的ADH3基因类型。除用聚合酶链式反应进行ADH3基因分型外，饮酒和脸红也用自我评估问卷进行评估。ADH3等位基因在对照组和受试组中的分布相当均匀。脸红在1/1男性中比2/2男性(两组)中更普遍。在这些女性中也发现了类似的关联倾向。在男性中，脸红倾向于与饮酒呈正相关，而在女性中，则相反。ADH3^*1等位基因几乎只在选定组中酗酒的男性中流行，报告了对酒精的异常反应。较少

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