PHENOBARBITAL, DRUG-METABOLISM, AND HUMAN CANCER

To investigate the possible influence of anticonvulsant treatment on c ancer risk, a nested case-control study of 104 lung cancers, 18 bladde r cancers, and 322 cancer-free controls was conducted. The background for the study was previous observations among 8004 epileptics in Denma rk with a significantly high risk for lung cancer and a significantly low risk for bladder cancer. Cigarette smoking appears to explain the lung cancer excess but not the low risk for bladder cancer, another to bacco-related disease. Information was abstracted on 94 and 95% of the cases and controls, respectively. Lung cancer was not associated with any anticonvulsant drug, but bladder cancer was inversely related to use of phenobarbital (PB). The apparent protective effect of PB was fu rther evaluated in a study of rats given 4-aminobiphenyl (ABP), a blad der carcinogen. The levels of 4-aminobiphenyl adducts in hemoglobin an d in bladder and liver DNA were significantly lower in rats given PB p rior to 4-aminobiphenyl, compared to controls. These studies suggest t hat PB may induce drug-metabolizing enzymes of the liver that deactiva te bladder carcinogens found in cigarette smoke and provide clues to t he role of activation and detoxification of carcinogens in humans.