Pharmacologic requirements for obtaining sensitization of human tumor cells in vitro to combined 5-fluorouracil or ftorafur and x rays
The combined effects of X ray and 5-Fluorouracil (5-FU) in tissue culture have been studied using two human adenocarcinonma lines (HeLa and HT-29 cells). Both showed similar sensitivities to 5-FU, HeLa cells appearing somewhat more resistant to higher concentrations. Combined treatment of both cell types with 5-FU and X rays led to a time-dependent enhancement of cell killing (''radiosensitization''). Only post-radiation incubation had any effect, prior exposure to 5-FU being strictly additive. Enhanced cell killing by combined 5-FU and X rays could not be explained by either the infliction of additional acute damage in the immediate post-radiation period or an inhibitory effect of 5-FU on the repair of sub-lethal X ray injury. Rather, the enhanced cytotoxicity proved to be dependent on a damage expressed in time periods exceeding the duration of a cell doubling time in vitro. Overall, the data equally suggest that X rays may sensitize the cells to 5-FU. The enhanced cell killing is maximized if the cells are continuously exposed to 5-FU for 48 hours following the X ray exposure. These results indicate that clinical treatment regimens might be useful in evaluating 5-FU infusional scheduling in accordance with these unique requirements, which are not met by conventional bolus 5-FU and X ray therapy fractionation regimens.Ftorafur, a drug proposed to act as a slow release form of 5-FU, was found to show limited cytotoxic potential in vitro and did not significantly enhance cell killing after X ray exposure.
- Research Organization:
- Univ. of California Medical School, La Jolla
- OSTI ID:
- 5403973
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8:11; ISSN IOBPD
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AZINES
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL KILLING
DRUGS
ELECTROMAGNETIC RADIATION
FLUOROURACILS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
IONIZING RADIATIONS
MAMMALS
MAN
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHARMACOLOGY
PRIMATES
PYRIMIDINES
RADIATIONS
RADIOINDUCTION
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RECOVERY
REPAIR
SYNERGISM
TUMOR CELLS
URACILS
VERTEBRATES
X RADIATION