Journal article
Down-regulation of c-myc gene expression with induction of high molecular weight DNA fragments by fluorodeoxyuridine
Biochemical pharmacology, Vol.48(2), pp.327-334
1994
DOI: 10.1016/0006-2952(94)90104-X
PMID: 8053928
Abstract
5-Fluoro-2′-deoxyuridine (FdUrd), a potent inhibitor of thymidylate synthase, induces extensive bulk DNA damage at drug concentrations that produce significant
in vitro growth inhibition of human ileocecal carcinoma (HCT-8) cells. Constant- and pulsed-field gel electrophoresis (CFGE and PFGE), to detect size distribution of DNA double-strand breaks and repair kinetics, in parallel with northern and western blot analyses, to quantitate
c-myc gene and protein expression, were utilized to analyze drug effects. At 24-hr post
in vitro drug treatment, when maximum bulk DNA damage was detected, FdUrd produced a broad range of high molecular weight DNA fragments, clustering between 0.1 and 5.7 megabases in size, and resulted in a decrease in the level of
c-myc transcripts and protein with no significant effect on the level of
v-myc and H-
ras. These effects preceded the observed cellular growth inhibition. Addition of the reduced folate leucovorin potentiated the effects induced by FdUrd, indicating that thymidylate synthase inhibition is an important initial step in drug effect followed by DNA fragmentation and suppression of
c-myc expression. Changes in the integrity of the genetic materials and regulatory genes occurred prior to the observed cell growth inhibition by FdUrd, suggesting that these molecular alterations by FdUrd may be associated with subsequent FdUrd-induced cell growth inhibition.
Details
- Title: Subtitle
- Down-regulation of c-myc gene expression with induction of high molecular weight DNA fragments by fluorodeoxyuridine
- Creators
- Li Zhan-Rong - Roswell Park Cancer InstituteYin Ming-Biao - Roswell Park Cancer InstituteMark A. Arredondo - Roswell Park Cancer InstituteChristoph Schöber - Roswell Park Cancer InstituteYoucef M. Rustum - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Biochemical pharmacology, Vol.48(2), pp.327-334
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0006-2952(94)90104-X
- PMID
- 8053928
- ISSN
- 0006-2952
- eISSN
- 1873-2968
- Language
- English
- Date published
- 1994
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359669502771
Metrics
5 Record Views