Variations in 5-Fluorouracil Concentrations of Colorectal Tissues as Compared with Dihydropyrimidine Dehydrogenase (DPD) Enzyme Activities and DPD Messenger RNA Levels

Dihydropyrimidine dehydrogenase (DPD) is the initial key enzyme in 5-fluorouracil (5-FU) catabolism. We measured DPD activities represented as DPD protein levels (units/mg protein) and the associated mRNA levels in tumorous and normal tissues from 40 colorectal cancer patients, and we studied the re...

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Bibliographic Details
Published in:Clinical cancer research 2001-09, Vol.7 (9), p.2783-2787
Main Authors: TANAKA-NOZAKI, Motoko, ONDA, Masahiko, TANAKA, Noritake, KATO, Shunji
Format: Article
Language:English
Subjects:
Antimetabolites, Antineoplastic - metabolism
Antimetabolites, Antineoplastic - therapeutic use
Antineoplastic agents
Biological and medical sciences
Chemotherapy
Colon - drug effects
Colon - metabolism
Colon - pathology
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Dihydrouracil Dehydrogenase (NADP)
Dose-Response Relationship, Drug
Female
Floxuridine - metabolism
Floxuridine - therapeutic use
Fluorouracil - metabolism
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Male
Medical sciences
Middle Aged
Oxidoreductases - drug effects
Oxidoreductases - genetics
Oxidoreductases - metabolism
Pharmacology. Drug treatments
Rectum - drug effects
Rectum - metabolism
Rectum - pathology
RNA, Messenger - drug effects
RNA, Messenger - genetics
RNA, Messenger - metabolism
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
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Summary:Dihydropyrimidine dehydrogenase (DPD) is the initial key enzyme in 5-fluorouracil (5-FU) catabolism. We measured DPD activities represented as DPD protein levels (units/mg protein) and the associated mRNA levels in tumorous and normal tissues from 40 colorectal cancer patients, and we studied the relation to 5-FU concentrations in the same samples after treatment with doxifluridine, a prodrug of 5-FU. DPD mRNA levels were also measured in biopsy samples before treatment for comparison with those in surgical samples. 5-FU 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 correlation ( 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 correlated with those in surgical specimens ( r = 0.366; P < 0.05). These results suggest DPD activities in tumors to be predictive of 5-FU levels in colorectal cancer tissues and are reflected by DPD mRNA levels as measured by reverse transcription-PCR.
ISSN:1078-0432
1557-3265