Wojciech Jelski

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the cancer diseases

Epidemiological data have identified chronic alcohol consumption as a significant risk factor for cancer in humans. The exact mechanism of ethanol-associated carcinogenesis has remained unknown. The metabolism of ethanol leads to generation of acetaldehyde (AA), which is highly toxic and carcinogenic. The amount of acetaldehyde to which cells or tissues are exposed after alcohol ingestion may be of great importance and may, among others, affects carcinogenesis. Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase (ADH). The enzyme responsible for oxidation of acetaldehyde is aldehyde dehydrogenase (ALDH). Both formation and degradation of acetaldehyde depends on the activity of these enzymes. The total alcohol dehydrogenase activity is significantly higher in cancer tissues than in this healthy organs (e.g. liver, stomach, esophagus, colorectum). Moreover the activity of ADH is much higher than the activity of ALDH. This suggests that cancer cells have a greater capability for ethanol oxidation but less ability to remove acetaldehyde than normal tissues. In addition significant differences of ADH isoenzymes activities between cancer tissues and healthy organs may be a factor intensifying carcinogenesis by the increased ability to acetaldehyde formation from ethanol and disorders in metabolism of some biologically important substances (e.g. retinoic acid). The changes in activity of particular ADH isoenzymes in the sera of patients with different cancers, seem to be caused by release of these isoenzymes from cancer cells, and may be useful for diagnostics of this cancer. The particular isoenzymes of ADH present in the serum may indicate the cancer localization.

Plasma apelin levels and apelin/APJ mRNA expression in patients with gestational diabetes mellitus

AIMS AND METHODS Apelin is a novel adipokine identified as an endogenous ligand of the G protein-coupled receptor APJ. In this study we compared plasma apelin concentrations in 101 patients with gestational diabetes (GDM) and 101 women with normal glucose tolerance (NGT) between 24 and 32 weeks of gestation (Group 1), as well as in 20 women with GDM and 16 subjects with NGT at term (Group 2). Apelin and APJ mRNA expression in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue were also measured in Group 2, using quantitative real-time PCR. RESULTS There were no significant differences in plasma apelin levels between the women with GDM and NGT (Group 1: 1555.6 [1281.2-1804.2]pg/ml vs 1656.5 [1430.2-1852.1]pg/ml, Group 2: 1607.9 [1453.4-1768.7]pg/ml vs 1493.8 [1316.8-1956.7]pg/ml) nor in apelin and APJ mRNA expression in SAT, VAT and placental tissue. Apelin mRNA expression was approximately 10 fold higher in placental than in adipose tissue (p<0.0001). Apelin and APJ mRNA expression correlated significantly in SAT (R=0.45, p=0.03), VAT (R=0.69, p=0.003) and placental tissue (R=0.37, p=0.03). CONCLUSIONS No associations between circulating apelin or apelin/APJ mRNA expression and GDM or the indices of insulin resistance were noted in our study.

The activity of class I, II, III, and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in colorectal cancer.

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 andbacteria. The enzyme responsible for oxidation of acetaldehyde is aldehyde dehydrogenase. Theaim of this study was to compare ADH isoenzymes and ALDH activity in colorectal cancer withthe activity in normal colonic mucosa. Total ADH activity was measured by a photometric methodwith p-nitrosodimethylaniline (NDMA) as substrate, and ALDH activity by a fluorometric methodwith 6-methoxy-2-naphthaldehyde as a substrate. For measurement of the activity of class I andII isoenzymes we employed fluorometric methods, with class-specific fluorogenic substrates. Theactivity 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 routineoperations of colorectal carcinomas from 32 patients. The activities of total ADH and, the mostimportant 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 inhealthy mucosa. ALDH activity was not significantly lower in the cancer cells. The activities of alltested enzymes and isoenzymes were not significantly higher in drinkers than in nondrinkers bothin colorectal cancer and in normal mucosa. The differences in activities of total ADH and class Iisoenzyme between cancer tissues and normal colon mucosa might be a factor for metabolic changesand disturbances in low-mature cancer cells and, additionally, might be a reason for the higher levelof acetaldehyde, which can intensify carcinogenesis.

The Activity of Class I, II, III, and IV Alcohol Dehydrogenase (ADH) Isoenzymes and Aldehyde Dehydrogenase (ALDH) in Liver Cancer

Background Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are most abundant in the liver, are the main enzymes involved in ethanol and acetaldehyde metabolism. Aims The purpose of this study was to compare the activity of ADH isoenzymes and ALDH between liver carcinoma cells and healthy hepatocytes. Patients Samples were taken from 44 liver cancer patients (19 drinkers, 25 nondrinkers). Seventeen patients had primary liver tumors and 27 had metastatic liver tumors. Methods Fluorimetric methods were used for measurement of the activity of class I and II ADH isoenzymes and ALDH activity. Total ADH activity and activity of class III and IV isoenzymes were measured by a photometric method. Results The activities of total ADH, ALDH, and class I ADH were significantly higher in cancer cells than in healthy tissues. The other tested classes of ADH showed a tendency toward higher activity in cancer than in normal cells. The differences between enzymes of drinkers and nondrinkers in both cancer and healthy tissue, were not significant. Conclusion Differences in the activities of total ADH, ALDH and class I ADH isoenzyme between cancer liver tissues and healthy hepatocytes might be a factor in ethanol metabolism disorders, which can intensify carcinogenesis.

Activity of class I, II, III, and IV alcohol dehydrogenase isoenzymes in human gastric mucosa.

The gastric alcohol dehydrogenase (ADH) plays an important role in the “first pass” metabolism of ethanol. Human ADH exists in multiple forms, grouped into six classes and located in different tissues. In present study we investigated the activity of four classes (I, II, III, and IV) of alcohol dehydrogenase isoenzymes in the different parts of stomach (corpus and antrum) in patients with suspected gastric ulcer. The aim of the study was assess the particular role of different classes of ADH in the gastric dehydrogenase activity. For the measurement of the activity of class I and class II isoenzymes, we employed new fluorometric methods with specific substrates. The activity of class III alcohol dehydrogenase was measured by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as a substrate, respectively. All biopsy specimens were taken from less changed areas of the antrum and body of the stomach of 68 patients suspected of having gastric ulcer. It was found that ADH IV (gastric) activity was the highest (14.76 ± 0.68 in the corpus of the stomach in men; and 7.61 ± 0.68 in women, respectively). The activity of the ADH III isoenzyme was lower than that of ADH IV. The activities of class I and II ADH isoenzymes were barely detectable. All tested classes of ADH had higher activity in the corpus than in the antrum and in males than in females. In conclusion, the most important form of gastric ADH is isoenzyme of class IV, less important is the isoenzyme of class III. ADH classes I and II seem to have no role in the stomach.

The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in breast cancer.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) play a significant role in the metabolism of many biological substances. ADH participates in the metabolism of ethanol, retinoic acid, lipid peroxidation products, leukotriene and glutathione metabolism. ALDH is responsible for oxidation of acetaldehyde and other aldehydes and metabolism of histamine and retinoic acid. The aim of this study was to compare the metabolism in breast cancer cells and normal breast parenchyma by measuring ADH isoenzymes and ALDH activities in these tissues. Total ADH activity was measured by a photometric method with p-nitrosodimethylaniline (NDMA) as a substrate. For the measurement of the activity of ALDH and class I and II isoenzymes of ADH we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III alcohol dehydrogenase was detected by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as substrates. The samples were taken surgically during resection of breast carcinoma from 75 women. The activity of the class I ADH isoenzyme was significantly lower in breast cancer cells than in healthy tissues. The other tested classes of ADH had a tendency for higher levels of activity in cancer cells than in normal mammary tissue. The activity of total ADH and ALDH was also not significantly lower in the cancer cells. The decrease of activity of class I ADH isoenzyme in breast cancer tissues may be a factor of some disorders in metabolic pathways with participation of these isoenzymes that can lead to carcinogenesis.

The activity of class I, II, III, and IV of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in pancreatic cancer.

Objectives: The pancreas can metabolize ethanol via oxidative pathway involving the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) as well as the nonoxidative pathway. In this study, we compared the activity of ADH isoenzymes and ALDH in the pancreatic cancer with the activity in normal tissue. In addition, the differences between enzyme activities of drinkers and nondrinkers were compared. Methods: For the measurement of the activity of class I and II ADH isoenzymes and ALDH activity, we used the fluorometric methods. The total ADH activity and activity of class III and IV isoenzymes were measured by the photometric method. The samples were taken from 56 pancreatic cancer patients (22 drinkers and 34 nondrinkers) and 56 healthy subjects. Results: The activity of class III ADH was significantly higher in cancer than in healthy tissues. Total activities of ADH and ALDH were not significantly different in cancer and normal cells. The differences between enzymes of drinkers and nondrinkers in both cancer and healthy tissue were not significant. Conclusion: Pancreatic cancer tissue exhibits higher activity of class III ADH isoenzyme than healthy tissue, and we consider that oxidative pathway of ethanol metabolism via ADH and ALDH does not play a role in pancreatic carcinogenesis.

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

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. J. Clin. Lab. Anal. 22:204–209, 2008.

The Activity of Class I, III, and IV of Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in Gastric Cancer

The metabolism of cancer is in many way different than in healthy cells. Increased metabolism of several carcinogenic substances may take place in cancer cells. The one of them was ethanol, that is oxidized by alcohol dehydrogenase (ADH) to high concentration of acetaldehyde, a toxic and carcinogenic compound. The enzyme responsible for oxidation of acetaldehyde is aldehyde dehydrogenase (ALDH). The aim of this study was to compare the capacity for ethanol metabolism measured by ADH isoenzymes and ALDH activity between gastric cancer and normal gastric mucosa. 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 isoenzymes, we used fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as a substrate. The samples were taken surgically during routine operations of gastric carcinomas from 55 patients. The activities of total ADH, and the most important in gastric mucosa, class IV ADH were significantly higher in cancer cells than in healthy tissues. The other tested classes of ADH and ALDH showed a tendency toward higher activity in cancer than in healthy mucosa. The activities of all tested enzymes and isoenzymes were not significantly higher in men than in women in wither gastric cancer tissues or normal mucosa. The increased ADH IV activity may be 1 of the factors intensifying carcinogenesis by the increased ability to acetaldehyde formation from ethanol.

Alcohol Dehydrogenase (ADH) Isoenzymes and Aldehyde Dehydrogenase (ALDH) Activity in the Human Pancreas

Ethanol metabolism in the pancreas occurs predominantly by way of an nonoxidative pathway to fatty acid ethyl esters but oxidative routes to acetaldehyde also may contribute to injury of pancreatic cells. Three metabolic systems are responsible for the oxidative metabolism of ethanol, among which the cytochrome P-4502E1 and alcohol dehydrogenase have been found in the pancreas. The aims of this study were to detect ADH and ALDH in the human pancreas and to assess which ADH isoenzymes are present in this organ. ADH activity was measured by the photometric method and ADH isoenzyme activity was determined using sensitive and specific substrates. ALDH activity was measured by the fluorometric method. We have shown that the activities of ADH and ALDH are present in the pancreas, although the activity of ALDH was not proportionally as low as ADH activity. The class III isoenzyme exhibited the highest activity of all ADH isoenzymes tested and it was about 7 times higher than the activity of class I. The activities of classes II and IV were low. The activities of ADH isoenzymes of classes I, II, and III in the pancreas of men were significantly higher than in women. This study demonstrates that alcohol dehydrogenase and aldehyde dehydrogenase are present in the pancreas.