Radiosensitization of hypoxic tumor cells by simultaneous administration of hyperthermia and nitroimidazoles. [X radiation]

Journal Article · Sun May 01 04:00:00 EDT 1977 · Radiat. Res.; (United States)

DOI:https://doi.org/10.2307/3574594· OSTI ID:7106899

Hofer, K G; Hofer, M G; Ieracitano, J; McLaughlin, W H

The radiation response of oxygenated and hypoxic L1210 leukemia cells subjected to in vivo treatments with hyperthermia and/or chemical radiosensitizers was evaluated with the (/sup 125/I)iododeoxyuridine prelabeling assay. X irradiation of L1210 cells at body temperatures of 41/sup 0/C or higher resulted in strongly enhanced tumor cell death. The magnitude of this thermal effect increased with increasing temperatures. Hypoxic L1210 cells were particularly sensitive to heat induced enhancement of radiation damage, i.e., the sensitizing effects were more pronounced and occurred at lower temperatures. Chemical radiosensitizers (metronidazole, Ro 7-0582) selectively sensitized hypoxic L1210 populations; fully oxygenated cells were not affected. Considerable radiosensitization was achieved at nontoxic dose levels of the two sensitizers. Experiments designed to determine the degree of radiosensititization as a function of drug dose showed that Ro 7-0582 was consistently more effective than metronidazole in sensitizing hypoxic tumor populations. At the highest drug dose used (3 mg/g body wt) the DMF was 2.2 for metronidazole and 2.8 for Ro 7-0582. Combined administration of hyperthermia and Ro 7-0582 (or metronidazole) produced synergistic potentiation of radiation damage in hypoxic L1210 populations (DMF of 4.2). Under optimal conditions, hypoxic L1210 cells subjected simultaneously to both modes of radiosensitization became more radiosensitive than untreated, fully oxygenated L1210 cells. Experiments on two other tumor lines (BP-8 murine sarcoma and Ehrlich ascites cells) indicate that such synergistic radiosensitization effects are not unique to L1210 cells.

• Research Organization: Florida State Univ., Tallahassee
• OSTI ID: 7106899
• Journal Information: Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 70:2; ISSN RAREA
• 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
ANOXIA
ANTIMETABOLITES
ANTIMITOTIC DRUGS
AZINES
AZOLES
BETA DECAY RADIOISOTOPES
BODY TEMPERATURE
CELL KILLING
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTROMAGNETIC RADIATION
ELECTRON CAPTURE RADIOISOTOPES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
HYPERTHERMIA
IMIDAZOLES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
IODODEOXYURIDINE
IODOURACILS
IONIZING RADIATIONS
ISOTOPE APPLICATIONS
ISOTOPES
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RADIATIONS
RADIOISOTOPES
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RESPONSE MODIFYING FACTORS
RIBOSIDES
TEMPERATURE DEPENDENCE
TRACER TECHNIQUES
TUMOR CELLS
URACILS
X RADIATION