The activity of class I, II, III, and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in colorectal cancer
The activity of class I, II, III, and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in colorectal cancer
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DOI：
10.1023/b:ddas.0000034557.23322.e0
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发表时间：
2004-06-01
影响因子：
3.1
通讯作者：
Szmitkowski, M
中科院分区：
文献类型：
--
作者：
Jelski, W;Zalewski, B;Szmitkowski, M
长期饮用酒精会增加患结直肠癌的风险。剧毒和致癌的化合物是乙醛，它是乙醇代谢的产物。在大肠粘膜和细菌中，乙醇被乙醇脱氢酶(ADH)代谢成乙醛。负责乙醛氧化的酶是乙醛脱氢酶。本研究的目的是比较结直肠癌和正常结肠粘膜的ADH同工酶和ALDH活性。以对亚硝酸二甲基苯胺(NDMA)为底物，用分光光度法测定ADH总活性；以6-甲氧基-2-萘醛为底物，用荧光法测定ALDH活性。为了测量I类和II类同工酶的活性，我们使用了荧光法，使用类特定的荧光底物。以正辛醇为底物，以间硝基苯甲醛为底物，用分光光度法测定了Ⅲ类ADH的活性。32例结直肠癌患者在常规手术中采集标本。癌组织中总ADH活性和结肠粘膜中最重要的I类ADH活性显著高于正常组织。其他受测类别的ADH在癌细胞中的活性水平有高于健康粘膜的趋势。癌细胞中的ALDH活性没有明显降低。无论是在结直肠癌还是在正常粘膜中，饮酒者所有被测试的酶和同工酶的活性都没有明显高于不饮酒者。癌组织和正常结肠粘膜中总ADH和I类同工酶活性的差异可能是低成熟癌细胞代谢改变和紊乱的一个因素，也可能是乙醛水平较高的原因之一，乙醛可以加剧癌变。
Chronic ethanol consumption is associated with an increased risk for cancer of the colorectum. The highly toxic and carcinogenic compound is acetaldehyde, the product of ethanol metabolism. Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase (ADH) in colorectal mucosa and bacteria. The enzyme responsible for oxidation of acetaldehyde is aldehyde dehydrogenase. The aim of this study was to compare ADH isoenzymes and ALDH activity in colorectal cancer with the activity in normal colonic mucosa. Total ADH activity was measured by a photometric method with p-nitrosodimethylaniline (NDMA) as substrate, and ALDH activity by a fluorometric method with 6-methoxy-2-naphthaldehyde as a substrate. For measurement of the activity of class I and II isoenzymes we employed fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with n-octanol as substrate, and class IV with m-nitrobenzaldehyde as substrate. Samples were taken surgically during routine operations of colorectal carcinomas from 32 patients. The activities of total ADH and, the most important in colon mucosa, class I ADH were significantly higher in cancer than in healthy tissues. The other tested classes of ADH had a tendency to higher-level activity in cancer cells than in healthy mucosa. ALDH activity was not significantly lower in the cancer cells. The activities of all tested enzymes and isoenzymes were not significantly higher in drinkers than in nondrinkers both in colorectal cancer and in normal mucosa. The differences in activities of total ADH and class I isoenzyme between cancer tissues and normal colon mucosa might be a factor for metabolic changes and disturbances in low-mature cancer cells and, additionally, might be a reason for the higher level of acetaldehyde, which can intensify carcinogenesis.