Effectof Methylprednisoloneon Cell Proliferationin C3H/HeJ SpontaneousMammaryTumors1

The presentstudieswere initiatedto investigatethe effectsof methylprednisolone (MP)onthegrowthandcell kineticsof 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. Cellkineticparameters weredeter minedbyIn vitromethodsafterMPevery12hrin3 doses. At bothdoselevelsa similar50%decreaseinthetritiated thymidinelabelingindexwas observed2 hr after treat ment.Atthistime,theprimer-dependent DNApolymerase labelingindex,an in vitroestimateof tumorgrowthfrac tion,wassimilarto untreatedcontrolsat bothdosebevels. ThecellkineticchangesafterMP(10mg/kgevery12hrin 3 doses)suggesteda reversibleG1blockwith synchro nous progressionof tumorcells throughthe cell cycle after cessationof treatment.While synchronywas also @ suggestedafter MP (20 mg/kg every 12 hr in 3 doses), resumptionof cell proliferationwas delayed by 18 hr. Treatmentwith5-fluorouracll andmethotrexate 12 hrafter cessationof MP (10mg/kgevery12 hr in3 doses),a time corresponding to maximaltritiatedthymidinelabelingin dex, resultedin greater tumor regressionand greater regrowth delay than did 5-fluorouracil and methotrexate given at times corresponding to low tritiatedthymidine labelingindexes.Tumor volume-doubling times during regrowthwere significantlylonger than either prior to treatmentor aftermethotrexate and5-fluorouracib alone.