Effects of orally administered 5-fluorouracil and its derivative 5'-deoxy-5-fluorouridine on 7,12-dimethylbenz[a]anthracene-induced breast carcinomas in rats.

Antitumour activity of 20 mg/kg 5-fluorouracil (5-FU) and 100 or 200 mg/kg 5'-deoxy-5-fluorouridine (5'-DFUR) was assessed by tumour regression, light and electron microscopic changes, and immunohistochemical variations in broxuridine labelling in 7,12-dimethyl-benz[a]anthracene- (DMBA-) induced breast carcinomas in rats. The relative regression of tumours was significantly (P less than 0.05) greater in animals receiving 5-FU or 5'-DFUR than in control animals. Light microscopic changes became apparent after 3 or 4 days' treatment and were more evident after 4-21 days. Electron microscopic degeneration of tumours was observed after 1 day. The broxuridine labelling index decreased significantly (P less than 0.05) in rats receiving 5-FU and especially in those receiving 5'-DFUR. Concentrations of 5-FU in DMBA-induced breast carcinomas were significantly (P less than 0.05) higher in rats treated with 5'-DFUR than in those treated with 5-FU, and the histological degeneration was significantly (P less than 0.05) more advanced in 5'-DFUR- than in 5-FU-treated animals, possibly due to the higher pyrimidine nucleoside phosphorylase activity in the former treatment group.