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Effect of Methylprednisolone on Cell Proliferation in C3H/HeJ Spontaneous Mammary Tumors¹

Cancer Research Unit, Division of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212

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.

¹ This investigationw as supported by Grant CA-10438 and BCTF Contract N01-CB-43899, awarded by the National Cancer Institute, Department of Health, Education and Welfare.

Received 3/ 2/78. Accepted 8/25/78.