Alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase activity in the sera of patients with esophageal cancer

Abstract

Various alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) exist in the human esophageal mucosa. In our last experiments we have shown that ADH and ALDH are present also in the esophageal cancer cells. Moreover, the activities of total ADH and class IV isoenzymes were significantly higher in cancer tissue than in healthy mucosa, which suggests that these changes may be reflected by enzyme activity in the serum. Therefore, we measured the activity of total alcohol dehydrogenase, and classes I-IV of this enzyme and aldehyde dehydrogenase in the sera of patients with this cancer. Serum samples were taken for routine biochemical investigation from 67 patients with esophageal cancer before treatment. Total ADH activity was measured by photometric method with p-nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde as a substrate. For the measurement of the activity of class I and II isoenzymes, we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III alcohol dehydrogenase was measured by the photometric method with formaldehyde and class IV with m-nitrobenzaldehyde as a substrate. A statistically significant increase of class IV alcohol dehydrogenase isoenzymes was found in the sera of cancer patients. The median activity of this class isoenzyme in the total cancer group increased by about 26.5% (7.42 mU/l) in comparison to the control level (5.46 mU/l). The total alcohol dehydrogenase activity was significantly higher (30%) among patients with cancer. The activities of other tested ADH isoenzymes and total ALDH were unchanged. The activity of the class I ADH isoenzyme was significantly higher in the sera of drinkers with esophageal cancer than non-drinking patients. The increased total activity of alcohol dehydrogenase and class IV isoenzyme in the sera of patients with esophageal cancer probably can be caused by release of this isoenzyme from cancer cells or might be stimulated by alcohol drinking.

The alcohol dehydrogenase isoenzyme (ADH IV) as a candidate tumour marker of esophageal cancer.

“…In our previous study we found that the total alcohol dehydrogenase activity was changed in the serum of patients with esophageal cancer. The increase intotal ADH activity was positively correlated with ADH IV implicating that the latter isoenzyme was mainly responsible for the increase of total serum alcohol dehydrogenase activity in the course of esophageal cancer (Jelski et al, 2009b). The present study is a continuation of our previous research.…”

“…The total ADH activity has been elevated in the sera of patients with esophageal cancer. The increase in total ADH activity was positively correlated with class IV ADH and seems to be caused by the release of this isoenzyme from the cancer tissue (Jelski et al, 2009b).…”

Distinct prognostic values of alcohol dehydrogenase mRNA expression in pancreatic adenocarcinoma

“…Both the serum and tissue expression level of class I and total ADH were significantly increased in liver,27,28 colorectal,29,30 and brain cancers,31,32 while ALDH levels were not statistically significant different between cancer patients and healthy subjects. The upregulation trend of class I ADH between cancer and healthy tissue can also be found in cervical,33 ovarian,34 endometrial,35 and renal cell cancers,36 whereas the upregulation trend of class I ADH for cancer serum has been reported in bladder and esophageal cancers 37,38. However, the expression of class I ADH in breast cancer was significantly decreased compared to the tissue of healthy subjects, and the expression of ALDH was unchanged 39.…”

Carcinogen in Alcohol, a Review

“…Various studies have pointed out that an imbalance between the activities of ADH and ALDH play a critical role in alcoholinduced neoplasm [33]. Essentially higher actions of different isoforms have been stated in esophageal cancer [34], liver cancer [35], and cervical cancer [36]. Acetaldehyde may be the significant cancer-causing agent in the upper and lower gastrointestinal tract, as acetaldehyde concentrations in saliva and in the large intestine are enough to facilitate in it and act as a carcinogen [37][38][39][40][41][42].…”