ALTERED HEME PATHWAY REGULATION AND DRUG-METABOLIZING ENZYME-SYSTEM IN A MOUSE MODEL OF HEPATOCARCINOGENESIS - EFFECT OF VERONAL

1. Male CF 1 mice were fed p-dimethylaminoazobenzene (DAB) for 35 days and received 5,5-diethylbarbituric acid, before or after DAB treatmen t, with the purpose of investigating whether the onset of the preiniti ation stage of carcinogenesis alters the natural regulatory mechanism of the heme pathway. 2. Changes detected in drug metabolizing enzymes are likely to be the consequence of a primary deregulation mechanism o f heme metabolism, shown by an increase in delta-aminolevulinic acid s ynthetase activity and a decrease in microsomal heme oxygenase, which would finally lead to a great enhancement of cytochrome P450 levels. 3 . The alterations found here would give rise to a pattern distinctive to that usually observed in the so called resistant hepatocyte. (C) 19 97 Elsevier Science Inc.