The Metabolism of Drugs by Hepatic Tumors*

Transformation from normal hepatic cell to tumor cell may be accompanied by a loss of ability to metabolize certain drugs by enzymes in the microsomal fraction. This change did not occur to any measurable extent during the "precancerous" stage; nor was it present in hepatic cells adjacent to the DAB-induced tumor. Only the neoplastic cell has lost this function--even severely damaged hepatic cells retained normal levels of metabolism of the drugs used in our experiments. The loss of enzyme activity in DAB-induced tumors was probably caused by an actual deficit of enzyme protein and not by a cofactor deficiency or by the presence of inhibitors in such tumors. Animals bearing hepatic tumors may be more "sensitive" than normal animals to some drugs. We have shown some tumor-bearing animals sleep longer after hexobarbital administration. Possible therapeutic implications are mentioned.