Effects of 5-fluorouracil derivative UFT on thymidylate synthetase and thymidine kinase in rat colorectal tumors.
BACKGROUND
Thymidylate synthetase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively.


METHODS
Weekly injections of 1,2-dimethyl-hydrazine induced high incidence of colorectal adenocarcinomas in rats.


RESULTS
An increased activity of thymidylate synthetase was found in the poorly differentiated adenocarcinomas of the chemically induced rat colorectal tumors. Six-week oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) reduced the total number of colorectal tumors, with the reduction of thymidylate synthetase activity in the poorly-differentiated type, though the mRNA expression of thymidylate synthetase and thymidine kinase differed little between the groups with or without UFT treatment.


CONCLUSIONS
These results indicate that the long-term oral administration using UFT suppresses colorectal carcinogenesis and the growth of the poorly-differentiated type tumors.
Sakamoto
S
S
Department of Surgery, School of Medicine, Tokyo Medical and Dental University, Japan. motoend@mri.tmd.ac.jp
Kawachi
Y
Y
Iwama
T
T
Kuwa
K
K
Suzuki
T
T
Mitamura
T
T
Kudo
H
H
Sassa
S
S
Yoshimura
S
S
Maemura
T
T
Nakayama
T
T
Ohsawa
M
M
Hara
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004338:Drug Combinations; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D005641:Tegafur / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism*; D014498:Uracil / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004338:Drug Combinations; D012333:RNA, Messenger; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase; D013937:Thymidine Kinase