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.
Sawada
Y
Y
Fourth Department of Internal Medicine, Hyogo College of Medicine, Japan.
Ohno
T
T
Shimoyama
T
T
Uematsu
K
K
Odagiri
H
H
D015127:9,10-Dimethyl-1,2-benzanthracene; D000284:Administration, Oral; D000818:Animals; D002843:Chromatin / Q000648:ultrastructure; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000627:therapeutic use*; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron; D008940:Mitotic Index; D010430:Pentosyltransferases / Q000032:analysis; D057845:Pyrimidine Phosphorylases; D051381:Rats; D011919:Rats, Inbred Strains; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
D002843:Chromatin; D005467:Floxuridine; D015127:9,10-Dimethyl-1,2-benzanthracene; D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases; D005472:Fluorouracil