Comparison of pyrimidine nucleotide synthetic enzymes involved in 5-fluorouracil metabolism between human adenocarcinomas and squamous cell carcinomas.
The activities of orotate phosphoribosyltransferase (OPRT), cytidine triphosphate (CTP) synthetase, deoxycytidine monophosphate (dCMP) deaminase, thymidine monophosphate (dTMP) kinase, uridine (Urd) kinase, thymidine (dThd) kinase, Urd and dThd phosphorylases, and DNA polymerase were examined in the eight human lung squamous cell carcinomas and five lung adenocarcinomas, and five tumor-adjacent normal lung tissues. All of these enzymes are involved in pyrimidine nucleotide synthesis. The metabolism of 5-fluorouracil (5-FU) was determined. The levels of these enzymes, except for OPRT, were high in tumor tissues and almost the same between lung squamous cell carcinomas and adenocarcinomas, with no statistical difference. The activities for phosphorylation and degradation of 5-FU were similar in each tissue type of tumor. As 5-FU is incorporated into tumor cells and is metabolized actively to 5-FU nucleotides in squamous cell carcinoma tissues, at almost the same level seen in adenocarcinoma tissues, this drug should have a wide clinical application.
Maehara
Y
Y
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Moriguchi
S
S
Emi
Y
Y
Watanabe
A
A
Kohnoe
S
S
Tsujitani
S
S
Sugimachi
K
K
D000230:Adenocarcinoma / Q000201:enzymology* / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000378:metabolism; D003844:DCMP Deaminase / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D008025:Ligases / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology* / Q000378:metabolism; D008875:Middle Aged; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism; D010766:Phosphorylation; D011742:Pyrimidine Nucleotides / Q000096:biosynthesis*; D013937:Thymidine Kinase / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000378:metabolism; D014541:Uridine Kinase / Q000378:metabolism; D014543:Uridine Phosphorylase / Q000378:metabolism
D011742:Pyrimidine Nucleotides; D009962:Orotate Phosphoribosyltransferase; D014543:Uridine Phosphorylase; D013939:Thymidine Phosphorylase; D013937:Thymidine Kinase; D014541:Uridine Kinase; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase; D004259:DNA-Directed DNA Polymerase; D003844:DCMP Deaminase; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase; D005472:Fluorouracil