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

已经证实，细胞色素P450同工酶在许多结构不同的化学物质向能够与细胞大分子反应的亲电试剂的代谢转化中很活跃。因此，致癌物原可以被生物活化为活性物质，并可以共价修饰染色体DNA，导致可能最终导致癌症的不可逆转的细胞变化。本研究的目的是估计乙醇对器官损伤的诱导程度，并阐明酒精对器官损伤的发生机制。采用逆转录- pcr （RT-PCR）方法检测不饮酒和习惯性饮酒的健康人CYP2E1mRNA水平，结果无统计学差异。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，ALDH2的三种基因型中CYP2E1mRNAin的表达水平也没有差异。结果表明，饮酒频率、频率和aldh2活性强弱对CYP2E1mRNA表达水平无明显影响。我们研究了芬兰人群中的ADH3多态性，以揭示ADH3基因型在酒精急性效应中的作用。我们分析了来自对照人群和对低酒精摄入量有异常反应的选定人群的ADH3基因型。除了用PCR检测ADH3基因型外，还采用自我评估问卷对饮酒和脸红进行评估。ADH3等位基因在对照组和选择组中的分布相当均匀。1/1组的男性比2/2组的男性（两组）脸红更普遍。在女性身上也可以看到类似的联系。在男性中，脸红倾向于与饮酒呈正相关，但在女性中则相反。ADH3^*1等位基因几乎只在被选中的酗酒男性中普遍存在，报告了对酒精的不寻常反应。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