Polyfunctional radiosensitizers. VII. Radiosensitization by conformationally-restricted isomers of a nitroxyl biradical in vitro

Journal Article · Tue Jan 01 04:00:00 EST 1985 · Radiat. Res.; (United States)

DOI:https://doi.org/10.2307/3576308· OSTI ID:5930479

Millar, B C; Jenkins, T C; Smithen, C E; Jinks, S

Both trans-N,N'-bis(2,2,6,6-tetramethyl-1-oxy-4-piperidinyl)-1,2-diaminocyclopropane(Ro31-2269) and its cis isomer (Ro 31-2778) selectively sensitized hypoxic Chinese hamster cells, line V-79-753B, to radiation by decreasing both the D/sub 0/ value and extrapolation number, whereas a related dibasic monoradical Ro 31-2655 decreased D/sub 0/ alone.There was no evidence for competition between either biradical and 2,2,6,6-tetramethyl-4-piperidinol-N-oxyl (TMPN) at equimolar concentration or biradical and 0.82 ..mu..M oxygen when cells were equilibrated with the biradicals for 3 hr prior to irradiation in the presence of mixtures of either oxygen and biradical, TMPN and biradical, or TMPN alone. Examination of the plasma membrane from cells equilibrated with the trans biradical Ro 31-2269 showed that the drug accumulated in the membrane when compared with the concentration found in whole cells. Experiments with the conformationally-unrestricted biradical bis(2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl) succinate (Ro 03-6061) showed that when cell were equilibrated with the compound for 1 hr prior to irradiation in hypoxia in the presence of a mixture containing an equimolar radical concentration of TMPN, there was an increase in both the slope and the extrapolation number compared with values for hypoxic cells irradiated in the presence of this biradical alone. The results are discussed in terms of a model to account for sensitization by these compounds.

• Research Organization: Inst. of Cancer Research, Sutton, England
• OSTI ID: 5930479
• Journal Information: Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 101:1; 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.
AMINES
ANIMAL CELLS
ANIMALS
ANOXIA
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CELL CONSTITUENTS
CELL KILLING
CELL MEMBRANES
COBALT 60
COBALT ISOTOPES
CONNECTIVE TISSUE CELLS
DATA
ELECTROMAGNETIC RADIATION
ELECTRON SPIN RESONANCE
EXPERIMENTAL DATA
FIBROBLASTS
GAMMA RADIATION
HAMSTERS
HETEROCYCLIC COMPOUNDS
INFORMATION
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IONIZING RADIATIONS
ISOMERIC TRANSITION ISOTOPES
ISOMERS
ISOTOPES
MAGNETIC RESONANCE
MAMMALS
MEMBRANES
MINUTES LIVING RADIOISOTOPES
NITROXYL RADICALS
NUCLEI
NUMERICAL DATA
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PIPERIDINES
PYRIDINES
RADIATIONS
RADICALS
RADIOINDUCTION
RADIOISOTOPES
RADIOSENSITIVITY EFFECTS
RESONANCE
RODENTS
SOMATIC CELLS
SURVIVAL CURVES
VERTEBRATES
YEARS LIVING RADIOISOTOPES