CHANGES IN HUMAN SERUM ALCOHOL-DEHYDROGENASE ACTIVITY DURING RETINOICACID TREATMENT OF CANCER-PATIENTS

Retinoids can inhibit cell growth and induce cell differentiation in e xperimental tumour models. Human alcohol dehydrogenase (ADH) exists as a group of enzymes that can be placed into five classes based upon st ructural 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 acti vity in human sera was determined. No significant changes in class I o r II activity were observed after 4 weeks of treatment with cis-retino ic acid (cRA). While total ADH activity was increased from 84 +/- 78 m U/l to 206 +/- 70 mU/l (mean +/- SD, P < 0.02) after 1 week of treatme nt, there were no further significant changes after 4 weeks of treatme nt with cRA. Sex-related differences were observed on total ADH activi ty after 1 week of treatment with cRA. Although total ADH activity of patients with cancer of the cervix increased significantly after 1 wee k of treatment, there were no significant changes in total activity in head and neck cancer patients. This sex-related difference might be d ependent on the stage of the menstrual cycle. The elimination of ethan ol in women can be either faster or slower than in men depending on th e stage of menstrual cycle. This study therefore suggests that the mai n 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 treatm ent.