Changes in thymidylate synthase mRNA in blood leukocytes from patients with colorectal cancer after bolus administration of 5-fluorouracil

Citation
E. Ehrnrooth et al., Changes in thymidylate synthase mRNA in blood leukocytes from patients with colorectal cancer after bolus administration of 5-fluorouracil, ACTA ONCOL, 39(1), 2000, pp. 53-57
Citations number
19
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ACTA ONCOLOGICA
ISSN journal
0284186X → ACNP
Volume
39
Issue
1
Year of publication
2000
Pages
53 - 57
Database
ISI
SICI code
0284-186X(2000)39:1<53:CITSMI>2.0.ZU;2-Z
Abstract
5-fluorouracil (5-FU) is considered the standard antineoplastic drug of cho ice for metastatic colorectal cancer. It has been suggested that 5-FU admin istered as bolus infusion is cytotoxic mainly through an RNA damaging effec t. We investigated the effect of i.v. bolus 5-FU 500-600 mg/m(2) on the 5-F U target enzyme, thymidylate synthase (TS) mRNA, in blood leukocytes before and after courses 1 and 3 in 21 patients with colorectal cancer. TS mRNA e xpression was quantified using an RT-PCR assay with an internal RNA standar d. Median TS mRNA expression decreased significantly 30 min after course no . 1 (p = 0.004), and both 15 min and 30 min after course 3 (p = 0.01). Afte r course 1, the median TS mRNA expression decreased by 31% and after course 3 by 24%. Pharmacokinetic parameters were similar for individual patients during the two courses but did not correlate with the degree of TS mRNA inh ibition. The present results indicate that TS mRNA in blood leukocytes may be an early indicator of an RNA damaging effect after i.v. bolus infusion o f 5-FU.