Lack of dependence of 5-fluorodeoxyuridine-mediated radiosensitization on cytotoxicity
- Univ. of Michigan Medical Center, Ann Arbor, MI (United States); and others
It has been proposed that fluoropyrimidine-mediated cytotoxicity and radiosensitization are closely correlated. We have shown that HT29 human colon cancer cells transfected with the E. coli dUTPase gene are resistant to 5-fluorodeoxyuridine (FdUrd)-mediated cytotoxicity, presumably through more effective elimination of dUTP. We used these cells to assess the association between radiosensitization and cytotoxicity produced by FdUrd. The radiation sensitivities of the clones expressing elevated dUTPase activity (dutE clones) were similar to those of untransfected HT29 cells or HT29 cells which has been transfected with only the expression vector for the E. coli gene (con clones). We found that FdUrd produced similar increases in radiation sensitivity regardless of dUTPase activity. Levels of dUTPase in the dutE clones remained elevated during the entire period of FdUrd exposure, demonstrating that the lack of difference between dutE and Con clones was not a reflection of down-regulation of dUTPase activity by FdUrd, Flow cytometry showed that all clones progressed past the G{sub 1}/S-phase boundary and into early S phase during FdUrd treatment. These data suggest that the mechanisms of FdUrd-mediated cytotoxicity and radiosensitization are not closely linked. These findings, combined with our previous investigations, are consistent with the hypothesis that radiosensitization occurs in cells which progress past the G{sub 1}/S-phase boundary in the presence of FdUrd. 24 refs., 2 figs., 2 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 146885
- Journal Information:
- Radiation Research, Journal Name: Radiation Research Journal Issue: 3 Vol. 143; ISSN RAREAE; ISSN 0033-7587
- Country of Publication:
- United States
- Language:
- English
Similar Records
Short Hairpin RNA Suppression of Thymidylate Synthase Produces DNA Mismatches and Results in Excellent Radiosensitization
Influence of cell cycle phase on radiation-induced cytotoxicity and DNA damage in human colon cancer (HT29) and Chinese hamster ovary cells
The role of cell cycle redistribution in radiosensitization: Implications regarding the mechanism of fluorodeoxyuridine radiosensitization
Journal Article
·
Fri Nov 30 23:00:00 EST 2012
· International Journal of Radiation Oncology, Biology and Physics
·
OSTI ID:22149687
Influence of cell cycle phase on radiation-induced cytotoxicity and DNA damage in human colon cancer (HT29) and Chinese hamster ovary cells
Journal Article
·
Thu Mar 31 23:00:00 EST 1994
· Radiation Research
·
OSTI ID:56780
The role of cell cycle redistribution in radiosensitization: Implications regarding the mechanism of fluorodeoxyuridine radiosensitization
Journal Article
·
Mon Nov 14 23:00:00 EST 1994
· International Journal of Radiation Oncology, Biology and Physics
·
OSTI ID:96062