Glucocorticoid effects of lymphosarcoma P1798 on DNA replication and growth of subcutaneous tumors in mice.

Injection of cortisol into BALB/c mice inhibited tritiated thymidine ([3H]dThd) incorporation into ascites cells of lymphosarcoma P1798 but not into cells isolated frm large subcutaneous tumors. The DNA synthetic index (SI), estimated autoradiographically after pulse labeling with [3H]dThd in vitro, was 0.25-0.29 for ascites cells and cells isolated from tumors having a radius squared (r2) less than 200 mm2. Cortisol decreased the SI of ascites cells by 90-95% within 5 hours. Similarly, cortisol decreased the SI of cells from subcutaneous tumors having an r2 less than 90 mm2. Growth and [3H]dThd incorporation were also inhibited by cortisol treatment of tumors with an r2 less than 90 mm2. However, when tumors became larger than 90 mm2, the SI did not decrease after cortisol treatment. Neither growth nor [3H]dThd incorporation was inhibited in tumors with an r2 greater than 90 mm2. These data indicate that tumors of lymphosarcoma P1798 became resistant to cortisol in a size-dependent manner. Loss of sensitivity ws not due to a gradual increase in the percentage of resistant cells.