Pharmacologic requirements for obtaining sensitization of human tumor cells in vitro to combined 5-fluorouracil or ftorafur and x rays

Journal Article · Sun Oct 31 23:00:00 EST 1982 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(82)90451-5· OSTI ID:5215835

Byfield, J E; Calabro-Jones, P; Klisak, I; Kulhanian, F

The combined effects of X ray and 5-fluorouracil (5-FU) in tissue culture have been studied using two human adenocarcinoma 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: 5215835
• 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

Related Subjects

560121* -- Radiation Effects on Cells-- External Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANTIMETABOLITES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL KILLING
DRUGS
ELECTROMAGNETIC RADIATION
FLUOROURACILS
HELA CELLS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
INHIBITION
INJURIES
IONIZING RADIATIONS
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RADIATION EFFECTS
RADIATION INJURIES
RADIATIONS
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RECOVERY
REPAIR
SYNERGISM
TISSUE CULTURES
TUMOR CELLS
URACILS
X RADIATION