title: Inhibition by 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene in rats.
abstract: It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). The administration of 3'-MeDAB in combination with 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) delayed the appearance of oval cells and the formation of hyperplastic nodules, which were observed in the liver from 3 and 5 weeks, respectively, after the onset of 3'-MeDAB feeding, and also delayed the transient increase of serum alpha-fetoprotein level, which transiently peaked at 5 weeks, and completely suppressed the transient increase of tissue thymidylate synthetase activity, but not thymidine kinase, which were induced by 3'-MeDAB at 5 weeks, and finally reduced markedly the incidence of hepatocarcinomas. These results indicate that the suppression of de novo synthesis in pyrimidine metabolism prevents hepatocarcinogenesis.
authors.affiliation: Medical Research Institute, Tokyo Medical and Dental University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sakamoto
authors.forename: H
authors.initials: H
authors.lastname: Hirai
authors.forename: H
authors.initials: H
authors.lastname: Taga
authors.forename: T
authors.initials: T
authors.lastname: Uchikoshi
authors.forename: T
authors.initials: T
authors.lastname: Sunaga
authors.forename: Y
authors.initials: Y
authors.lastname: Endo
authors.forename: H
authors.initials: H
authors.lastname: Kudo
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: N
authors.initials: N
authors.lastname: Kasahara
authors.forename: K
authors.initials: K
authors.lastname: Kuwa
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008749:Methyldimethylaminoazobenzene; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D005641:Tegafur / Q000627:therapeutic use*; D013937:Thymidine Kinase / Q000032:analysis; D014498:Uracil / Q000627:therapeutic use*; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins; D005641:Tegafur; D008749:Methyldimethylaminoazobenzene; D014498:Uracil; D013937:Thymidine Kinase