Effect of methylprednisolone on cell proliferation in C3H/HeJ spontaneous mammary tumors.

The present studies were initiated to investigate the effectsof methylprednisolone(MP)onthe growthandcell kinetics of C3H/HeJ spontaneousmammarytumor. MP given every 12 hr in 9 doses at 10 or 20 mg/kg/dose resulted In temporary stasis of tumor growth with liftle or novolumeregression.Cell kineticparameterswere deter minedbyIn vitromethodsafter MP every12 hr in 3 doses. At bothdose levels a similar50%decrease inthe tritiated thymidine labeling index was observed 2 hr after treat ment.Atthistime, the primer-dependentDNApolymerase labelingindex, an in vitroestimateof tumorgrowthfrac tion,was similarto untreatedcontrolsat bothdosebevels. The cell kineticchangesafter MP (10mg/kgevery 12 hr in 3 doses) suggesteda reversibleG1blockwith synchro nous progressionof tumor cells throughthe cell cycle after cessation of treatment. While synchronywas also @ suggestedafter MP (20 mg/kg every 12 hr in 3 doses), resumptionof cell proliferationwas delayed by 18 hr. Treatmentwith5-fluorouracllandmethotrexate12 hrafter cessationof MP (10 mg/kg every 12 hr in 3 doses),a time correspondingto maximaltritiated thymidinelabeling in dex, resulted in greater tumor regression and greater regrowth delay than did 5-fluorouracil and methotrexate given at times correspondingto low tritiated thymidine labeling indexes. Tumor volume-doublingtimes during regrowth were significantlylonger than either prior to treatmentor after methotrexateand 5-fluorouracibalone.