ALTERED AROMATIC AMINE METABOLISM IN EPILEPTIC PATIENTS TREATED WITH PHENOBARBITAL

The fate of carcinogens differs among individuals who have different a ctivities of drug-metabolizing enzymes that are important in activatin g and detoxifying carcinogens, A drug that profoundly alters the metab olism of drugs and carcinogens is the anticonvulsive agent phenobarbit al. To investigate why epileptic patients appear to have a low risk of cancer of the urinary bladder, and on the basis of the observation th at levels of aromatic amine-hemoglobin adducts are strongly associated with various risk factors for cancer at that site, we determined arom atic amine-hemoglobin adducts in 62 epileptic patients as a surrogate measure of the reaction of carcinogenic metabolites with DNA in target tissue, Although adducts were detected in all subjects, the levels we re proportional to daily tobacco consumption, When the subjects were s tratified into groups smoking 20 g tobacco/day or more, smoking <20 g/ day, and not smoking, an effect of medication was detected, Epileptic patients treated chronically with phenobarbital or primidone, which is effectively metabolized to phenobarbital, were found to have lower le vels of 4-aminobiphenyl adducts than patients on the other treatment ( P = 0.02; ANOVA), In nonsmokers, no effect of medication could be demo nstrated above background variation; however, an increasing effect was seen with tobacco consumption with only one-half the increase in addu cts per g of tobacco smoked as epileptic patients on other treatment, The difference in the increases (slopes of regression lines) was highl y significant statistically, This reduction in the level of hemoglobin -aromatic amine adducts is probably due to induction of detoxification enzymes in the patients treated with phenobarbital.