Effect of a combined administration of 5-fluorouracil and medroxyprogesterone acetate on pyrimidine nucleoside phosphorylases and thymidylate synthetase in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors

The effect of a combined therapy of medroxyprogesterone acetate (MPA) and 5 -fluorouracil (5-FU) on tumor size, pyrimidine nucleoside phosphorylase (Py NPase) activity, and thymidylate synthetase (TS) activity was examined in S prague-Dawley (SD) rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. MPA augmented the antitumor activity of 5-FU and protected against body weight-loss due to 5-FU administration. PyNPase activity of bo th the MPA group and the MPA+5-FU group tended to increase compared with th at of the 5-FU alone group. TS inhibition levels in the MPA+5-FU group tend ed to increase compared with those in the 5-FU alone group. These results i ndicate that MPA tended to augment antitumor activity of 5-FU and to reduce the side effects caused by 5-FU.