Effect of Methylprednisolone on Cell Proliferation in C3H/HeJ Spontaneous Mammary Tumors

The present studies were initiated to investigate the effects of methylprednisolone (MP) on the growth and cell kinetics of C3H/HeJ spontaneous mammary tumor. MP given every 12 hr in 9 doses at 10 or 20 mg/kg/dose resulted in temporary stasis of tumor growth with little or no volume regression. Cell kinetic parameters were determined by in vitro methods after MP every 12 hr in 3 doses. At both dose levels a similar 50% decrease in the tritiated thymidine labeling index was observed 2 hr after treatment. At this time, the primer-dependent DNA polymerase labeling index, an in vitro estimate of tumor growth fraction, was similar to untreated controls at both dose levels. The cell kinetic changes after MP (10 mg/kg every 12 hr in 3 doses) suggested a reversible G1 block with synchronous progression of tumor cells through the cell cycle after cessation of treatment. While synchrony was also suggested after MP (20 mg/kg every 12 hr in 3 doses), resumption of cell proliferation was delayed by 18 hr. Treatment with 5-fluorouracil and methotrexate 12 hr after cessation of MP (10 mg/kg every 12 hr in 3 doses), a time corresponding to maximal tritiated thymidine labeling index, resulted in greater tumor regression and greater regrowth delay than did 5-fluorouracil and methotrexate given at times corresponding to low tritiated thymidine labeling indexes. Tumor volume-doubling times during regrowth were significantly longer than either prior to treatment or after methotrexate and 5-fluorouracil alone.