Initial and early effects of adriamycin in murine sarcoma 180 cannot be restored in a resistant subline by increasing the uptake and external concentration of the drug.

We demonstrate the early effects (1 day) of Adriamycin (ADM) on proliferation-stimulated and quiescent sensitive, and ADM-resistant cells of the murine tumor sarcoma 180 (S 180). By investigating cell-cycle distribution and thymidine labeling, it can be shown that sensitive cells are strongly affected by the drug, even in a proliferationarrested state. A remarkable but slow DNA synthesis is the prominent effect of this drug treatment on sensitive cells, even under nonstimulating conditions. In resistant cells, neither an increase in concentration nor a variation in drug uptake can induce effects that could be compared with those observed in the sensitive line. From these results we conclude that the early effects of ADM are not modulated by drug uptake.