Changes in human serum alcohol dehydrogenase activity during retinoic acid treatment of cancer patients

Retinoids can inhibit cell growth and induce cell differentiation in experimental tumour models. Human alcohol dehydrogenase (ADH) exists as a group of enzymes that can be placed into five classes based upon structural and functional distinctions. Human class I ADH catalyses the oxidation of a wide variety of alcohols including ethanol and retinol, whereas human class II ADH does not catalyse the oxidation of retinol. Using specific fluorescent substrates, class I and class II ADH activity in human sera was determined. No significant changes in class I or II activity were observed after 4 weeks of treatment with cis-retinoic acid (cRA). While total ADH activity was increased from 84 +/- 78 mU/1 to 206 +/- 70 mU/1 (mean +/- SD, P < 0.02) after 1 week of treatment, there were no further significant changes after 4 weeks of treatment with cRA. Sex-related differences were observed on total ADH activity after 1 week of treatment with cRA. Although total ADH activity of patients with cancer of the cervix increased significantly after 1 week of treatment, there were no significant changes in total activity in head and neck cancer patients. This sex-related difference might be dependent on the stage of the menstrual cycle. The elimination of ethanol in women can be either faster or slower than in men depending on the stage of menstrual cycle. This study therefore suggests that the main ADH activity observed in serum belongs to class II, and not to class I ADH. The data from this study also suggest that retinoic acid has a positive feedback effect on total ADH activity after 1 week of treatment.