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肝癌患者血清中的乙醇脱氢酶(ADH)同工酶及乙醛脱氢酶(ALDH)活性

Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with liver cancer.

作者信息

Jelski Wojciech, Zalewski Bogdan, Szmitkowski Maciej

机构信息

Department of Biochemical Diagnostics, Medical University, Waszyngtona 15A, Bialystok, Poland.

出版信息

J Clin Lab Anal. 2008;22(3):204-9. doi: 10.1002/jcla.20241.

Abstract

The principal enzymes catalyzing the conversion of ethanol to acetate are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). The activities of these enzymes are elevated in the serum during the course of alcoholism or cirrhosis. In previous investigations we have found elevated levels of ADH, ALDH, and class I ADH activity in liver cancer cells. It can suggest that these changes may be reflected by enzyme activity in the serum. In this work, the activity of ADH isoenzymes, and ALDH in the sera of patients with liver cancer was measured. Serum samples were taken from 64 patients (28 drinkers, 36 nondrinkers), with liver cancer. 25 patients had primary and 39 metastatic liver tumors. Total ADH activity was measured by photometric method with p-nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the fluorimetric method with 6-methoxy-2-naphtaldehyde as a substrate. For the measurement of the activity of class I and II isoenzymes we employed the fluorimetric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with formaldehyde and class IV with m-nitrobenzaldehyde as a substrate. A statistically significant increase of class I ADH isoenzymes was found in the sera of cancer patients. The median activity of this class isoenzyme in the total cancer group increased about 51% (2.94 mU/L) in the comparison to the control level (1.43 mU/L). The activity of the class I ADH isoenzyme was significantly higher in the sera of patients with metastatic tumors than with primary cancers. The activity of this class in the sera of drinkers and group of moderate drinkers was significantly higher in comparison to the control group and higher in the sera of heavy drinkers when compared with moderate drinking patients. The total ADH activity was significantly higher (44%) among patients with cancer than healthy ones. The activity of class I ADH isoenzymes was elevated only in the serum of patients with metastatic liver cancer. This increase of activity seems to be caused by the enzyme released from liver cancer cells and primary tumors originating in other organs.

摘要

催化乙醇转化为乙酸的主要酶是乙醇脱氢酶(ADH)和乙醛脱氢酶(ALDH)。在酒精中毒或肝硬化过程中,这些酶的活性在血清中会升高。在先前的研究中,我们发现肝癌细胞中ADH、ALDH和I类ADH活性水平升高。这可能表明这些变化可以通过血清中的酶活性反映出来。在这项工作中,我们测量了肝癌患者血清中ADH同工酶和ALDH的活性。血清样本取自64例肝癌患者(28例饮酒者,36例不饮酒者)。25例为原发性肝癌,39例为转移性肝癌。总ADH活性采用以对亚硝基二甲基苯胺(NDMA)为底物的光度法测定,ALDH活性采用以6-甲氧基-2-萘醛为底物的荧光法测定。对于I类和II类同工酶活性的测定,我们采用荧光法,使用类特异性荧光底物。III类ADH活性采用以甲醛为底物的光度法测定,IV类采用以间硝基苯甲醛为底物的光度法测定。在癌症患者血清中发现I类ADH同工酶有统计学意义的升高。与对照水平(1.43 mU/L)相比,该类同工酶在整个癌症组中的中位活性增加了约51%(2.94 mU/L)。转移性肿瘤患者血清中I类ADH同工酶的活性显著高于原发性癌症患者。与对照组相比,饮酒者和中度饮酒组血清中该类同工酶的活性显著更高,与中度饮酒患者相比,重度饮酒者血清中该类同工酶的活性更高。癌症患者的总ADH活性显著高于健康人(44%)。I类ADH同工酶的活性仅在转移性肝癌患者的血清中升高。这种活性增加似乎是由肝癌细胞和源自其他器官的原发性肿瘤释放的酶引起的。

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