Mixed-function oxidase enzymes in adriamycin-sensitive and resistant sublines of P-388 leukemia.

Levels of mixed-function oxidase (MFO) enzymes were measured in adriamycin(ADR)-sensitive murine leukemia P-388 and its ADR-resistant subline P-388/ADR. The subcellular fractions of the resistant cells showed decreased contents of MFO components, cytochrome P-450 and cytochrome b5, in comparison with the identically prepared fractions of the parental tumor. Similarly, the levels of 7-ethoxycoumarin O-deethylase and the rate of ascorbate induced lipid peroxidation in vitro showed lower values in resistant tumor cells than those of P-388 tumor cells. The observed differences in the two tumor cell types were found to be considerably enhanced if the tumor cells were exposed in vitro to ADR before fractionation. The magnitude of induction of the MFO enzymes was significantly greater in the ADR exposed P-388 cells. The corresponding inducibility was suppressed in the drug exposed resistant tumor cells.