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The Binding and Metabolism of Cortisol-4-C¹⁴ by Lymphatic Tissue and Tumors of Rats and Mice

( Cancer Research Centre, University of British Columbia, Vancouver, B. C., Canada)

The varied responses of thymus, spleen, and several tumors of rats and mice to cortisol treatment were compared with the capacity of these tissues to bind and to metabolize labeled cortisol. Dehydrogenation at C-11 and to a lesser extent removal of the side chain occurred upon incubation of cortisol-4-C¹⁴ with mouse thymus and spleen and malignant lymphocytes, including AKR mouse lymphatic leukemia, P1798 mouse lymphosarcoma—both steroid-sensitive and -resistant sublines—and LK2 rat lymphatic leukemia. The rat tumor and also rat thymus and IRC granulocytic leukemia showed little activity, and a chloroleukemia and several rhabdomyosarcomas showed no demonstrable metabolism. Cell suspensions incubated with cortisol-4-C¹⁴, centrifuged, and washed were all found to bind labeled steroid to the same extent. Unchanged cortisol was identified as the major or only component thus bound. It was concluded that the development of resistance to corticosteroids in tumors could not be attributed to differences in the binding or metabolism of cortisol, since no correlation between these processes and the response of tissue to cortisol in vivo was demonstrated.

Received 9/30/63.