Alcohol dehydrogenase and aldehyde dehydrogenase in malignant neoplasms

According to International Agency for Research on Cancer, ethanol and acetaldehyde belong to group 1 of human carcinogens. The accurate mechanism by which alcohol consumption enhances carcinogenesis is still unexplained. Alcohol is oxidized primarily by alcohol dehydrogenase (ADH) to acetaldehyde, a substance capable of initiating carcinogenesis by forming adducts with proteins and DNA and causing mutations. Next, acetaldehyde is metabolized by aldehyde dehydrogenase (ALDH) to acetate. In tissues of many cancers, we can observe significantly higher activity of total alcohol dehydrogenase with any change in aldehyde dehydrogenase activity in comparison with healthy cells. Moreover, in malignant diseases of digestive system, significantly increased activity of ADH isoenzymes class I, III and IV was found. The gynecological, brain and renal cancers exhibit increased activity of class I ADH. ADH and ALDH can play also a crucial regulatory role in initiation and progression of malignant diseases by participation in retinoic acid synthesis and elimination of toxic acetaldehyde. Besides, changes of enzymes activities in tumor cells are reflected in serum of cancer patients, which create the possibilities of application ADH isoenzymes as cancer markers.