Upregulation of enzymes metabolizing 5-fluorouracil in colorectal cancer.
BACKGROUND
The purpose of this study was to compare the activities of various enzymes, participating in the metabolism of 5-fluorouracil, between colorectal cancer and nontumor tissues and to investigate the association of the enzyme activities with clinicopathological backgrounds.


METHODS
Activities of seven enzymes involved in nucleic acid metabolism--orotate phosphoribosyltransferase (OPRT), ribonucleotide reductase (RNR), thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, uridine phosphorylase and thymidine kinase (TK)--were measured in tumor and nontumor tissues from 28 patients who were operated on for colorectal cancers.


RESULTS
OPRT, thymidylate synthase, RNR, thymidine phosphorylase, uridine phosphorylase and thymidine kinase activities were significantly higher in tumor areas than in nontumor areas. OPRT showed the highest T/N ratio (the ratio of each enzyme activity in tumor areas to that in nontumor areas). The T/N ratio of RNR activity showed a tendency to be associated with lymph node metastasis and Dukes classification.


CONCLUSIONS
The results suggest that OPRT is a main enzyme participating in the phosphorylation of 5-fluorouracil and has an important role in tumor growth. The T/N ratio of RNR may be predictive of tumor progression.
Matsusaka
Satoshi
S
Department of Hygiene and Preventive Medicine, Yamagata University School of Medicine, Yamagata, Japan.
Yamasaki
Hajime
H
Fukushima
Masakazu
M
Wakabayashi
Ichiro
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000201:enzymology*; D005260:Female; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000032:analysis / Q000378:metabolism*; D010766:Phosphorylation; D012264:Ribonucleotide Reductases / Q000032:analysis / Q000378:metabolism; D014166:Transferases / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation
D000964:Antimetabolites, Antineoplastic; D012264:Ribonucleotide Reductases; D014166:Transferases; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil