Inhibition by 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene in rats.
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.
Sakamoto
S
S
Medical Research Institute, Tokyo Medical and Dental University, Japan.
Hirai
H
H
Taga
H
H
Uchikoshi
T
T
Sunaga
T
T
Endo
Y
Y
Kudo
H
H
Kato
T
T
Kasahara
N
N
Kuwa
K
K
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
D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins; D005641:Tegafur; D008749:Methyldimethylaminoazobenzene; D014498:Uracil; D013937:Thymidine Kinase