Conditional oncogenicity of perfused adriamycin in the tourniquet-isolated rat limb

In an in vivo model for isolated limb perfusion, developed previously, adriamycin was observed to induce tumors, mainly rhabdomyosarcomas. The tumor incidence was dose dependent. A low incidence was observed after a pseudophysiological perfusion at low flow rate (LF) and 0.25 hematocrit (LF.25). The drug disappearance from the perfusate at the tumorigenic dose for LF.25 was studied in connection with the drug disappearance at two conditions with a high flow rate (HF) that differed from each other in oxygen supply and hematocrit (0.25, 0.11; codes: HF.25 and HF.11). A similar level of drug disappearance resulted in a tumor in six out of 12 limbs after HF.25 and eight out of 19 HF.11 perfused limbs but in only one tumor in 12 rats after LF.25 perfusion. A mechanism by which the HF perfusion conditions favor the induction of a tumor by adriamycin in perfused skeletal muscle remains to be defined.