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 from 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 was not due to a gradual increase in the percentage of resistant cells.—JNCl 65: 477-483, 1980.