Effects of intravenous and intracutaneous bacillus Calmette-Guérin application on the drug-metabolizing system of the liver.

Both single intravenous and repeated intracutaneous injections of bacillus Calmette-Guérin (BCG) resulted in alteration of the hepatic microsomal drug-metabolizing enzymes of the rat liver. The cytochrome P-450 content was not significantly altered; its activity (ethoxycoumarin O-dealkylation) was inhibited in both the intravenous and intracutaneous group. The arylhydrocarbon-hydroxylase and aminopyrine-demethylase activities were also diminished; decrease of cytochrome-c-reductase activity was noted after intravenous application only. Comparison of the results for the intravenous and intracutaneous application routes respectively showed qualitative and quantitative differences. The inhibitory effects of BCG treatment on the drug-metabolizing enzymes of the rat liver can only partly be explained by changes in the cytochrome P-450 system. These findings might lead to reconsideration of dosage of drugs in cancer (malignant melanoma) patients treated by combined chemoimmunotherapy.