[Anti-tumor effect of fluoropyrimidines on human tumor cell lines transplanted in nude mice with CCl4-induced liver dysfunction].
Tegafur (FT) is a masked compound of 5-fluorouracil (5-FU) and supposed to be activated in the liver. The present study was designed to estimate anti-tumor effect of FT on human tumors transplanted in nude mice with liver dysfunction induced by CCl4. Histologically, cirrhotic changes of liver were observed after injection with 1ml/kg 10% CCl4 twice a week for 8 weeks. Mice were transplanted with human gastric (GC-SF) or colonic cancer (CC-ZK) lines, and daily administered intragastrically with 5-FU (15mg/kg), FT (100mg/kg) or UFT (FT 20mg/kg + Uracil 44.8mg/kg) for 4 weeks. The growth of GC-SF was enhanced by liver dysfunction, but that of CC-ZK was not affected. The mean growth inhibition rates (MGIR) of CC-ZK by 5-FU, FT or UFT were 18.3, 33.1 and 54.2%, respectively, in mice without liver dysfunction, and 14.0, 50.0 and 59.5%, respectively, in mice with liver dysfunction. The MGIRs of GC-SF were 39.0, 63.8 and 48.0%, respectively, in mice without liver dysfunction, and 12.6, 53.6 and 50.0%, respectively, in mice with liver dysfunction. In both lines effect of 5-FU was reduced in liver dysfunction, but those of FT and UFT was not. These results suggest that FT and UFT can be used for cancer patients with liver dysfunction.
Nio
Y
Y
First Department of Surgery, School of Medicine, Kyoto University, Japan.
Imai
S
S
Shiraishi
T
T
Ohgaki
K
K
Tobe
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002251:Carbon Tetrachloride; D002460:Cell Line; D003110:Colonic Neoplasms / Q000150:complications / Q000188:drug therapy*; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000150:complications / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014498:Uracil / Q000008:administration & dosage
D005641:Tegafur; D014498:Uracil; D002251:Carbon Tetrachloride; D005472:Fluorouracil