ADDITIVE EFFECTS OF MEDROXYPROGESTERONE ACETATE AND 5-FLUOROURACIL DERIVATIVE ON 7,12-DIMETHYLBENZ[A]ANTHRACENE-INDUCED RAT MAMMARY-TUMORS

Chronic oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil suppressed thymidylate syntetase (TS) gene ex pression followed by reduction of TS activity in rat mammary tumors in duced with 7,12-dimethyl-benz[a]anthracene. Addition of medroxyprogest erone acetate (MPA) to the anticancer drug caused an additional decrea se in TS and thymidine kinase activities in the tumor growth and resto ration of bone loss. These results suggest that the simultaneous admin stration of MPA and anticancer drugs causes increased inhibition of ma mmary tumor growth and also diminishes the bone loss. [(C) 1998 Lippin cott-Raven Publishers.].