Depression of liver drug metabolism in sarcoma-bearing mice. Evidence for a circulating factor and dissociation from lipolytic activity.

Mice bearing the S-180 sarcoma displayed a depression of liver catalase and cytochrome P-450-dependent enzymes (ethoxycoumarin deethylase, ED) from day 6 following tumor implantation. Injection of serum obtained from tumor-bearing mice into normal mice caused depression of liver ED suggesting that a circulating factor was involved. Tumor-bearing mice did not show any significant change in serum triglycerides and food intake. By contrast, injection of endotoxin, interleukin-1 (IL-1) or tumor necrosis factor (TNF) caused not only a depression in liver ED but also a marked increase in serum triglycerides. To study the possible analogies between cancer-associated circulating factor and monokines, we studied the effect of dexamethasone (a known inhibitor of monokine synthesis) on liver ED activity in tumor-bearing mice. Dexamethasone (DEX) treatment increased (up to 60%) liver ED activity in tumor-bearing mice. We conclude that: (i) a circulating factor is involved in cancer-associated ED depression; (ii) that this mediator is not necessarily identical to TNF or IL-1 and (iii) that DEX reverses the depression of liver ED in cancer, possibly by inhibiting the synthesis, or the effects, of this factor.