Variations in 5-fluorouracil concentrations of colorectal tissues as compared with dihydropyrimidine dehydrogenase (DPD) enzyme activities and DPD messenger RNA levels

Citation
M. Tanaka-nozaki et al., Variations in 5-fluorouracil concentrations of colorectal tissues as compared with dihydropyrimidine dehydrogenase (DPD) enzyme activities and DPD messenger RNA levels, CLIN CANC R, 7(9), 2001, pp. 2783-2787
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
9
Year of publication
2001
Pages
2783 - 2787
Database
ISI
SICI code
1078-0432(200109)7:9<2783:VI5COC>2.0.ZU;2-4
Abstract
Dihydropyrimidine dehydrogenase (DPD) is the initial key enzyme in 5-fluoro uracil (5-FU) catabolism. We measured DPD activities represented as DPD pro tein levels (units/mg protein) and the associated mRNA levels in tumorous a nd normal tissues from 40 colorectal cancer patients, and we studied the re lation to 5-FU concentrations in the same samples after treatment with doxi fluridine, a prodrug of 5-FU. DPD mRNA levels were also measured in biopsy samples before treatment for comparison with those in surgical samples. 5-F U concentrations in tumors were higher than those in normal tissues (P < 0. 05) and were inversely associated with DPD protein levels (r = -0.463; P < 0.05). DPD activities in tumorous and normal tissues showed a significant c orrelation (r = 0.527; P < 0.01). DPD protein levels correlated with their mRNA levels detected by semiquantitative reverse transcription-PCR in tumor tissues (r = 0.740; P < 0.01). DPD mRNA levels in tumor biopsy specimens c orrelated with those in surgical specimens (r =: 0.366; P < 0.05). These re sults suggest DPD activities in tumors to be predictive of 5-FU levels in c olorectal cancer tissues and are reflected by DPD, mRNA levels as measured by reverse transcription-PCR.