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Studies on the mechanisms of the radiosensitizing and cytotoxic properties of RSU-1069 and its analogues

Journal Article · · Int. J. Radiat. Oncol., Biol. Phys.; (United States)
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RSU 1069 is a substantially more efficient sensitizer than misonidazole when hypoxic Chinese hamster V79 cells are irradiated in vitro at room temperature; such that for 0.5 mmol dm-3 sensitizer an ER of 3.0 is obtained for RSU 1069 whereas an ER of only 1.6 is obtained for misonidazole. However, when irradiation is done at 4/sup 0/C, the radiosensitization caused by RSU 1069 is reduced to a level close to that obtained with misonidazole, the action remaining unaltered at the lower temperature. This temperature dependent component of sensitization for RSU 1069 suggests the involvement of a slow biochemical process that has an appreciable activation energy. The RSU 1069 analogue RB 7040 is a more efficient radiosensitizer than RSU 1069 particularly at lower concentrations. This compound has a pKa value of 8.45, in contrast to that of RSU 1069 which is 6.04. Weak bases with pKa values in excess of average intra-cellular pH can be taken up preferentially into cells from medium at pH 7.4. It is shown that RB 7040 has a 4 X higher intracellular concentration than RSU 1069 for a similar extracellular concentration. This will explain, at least in part, the greater sensitizing efficiency of this compound when compared to RSU 1069 in vitro.

Research Organization:
M.R.C. Radiobiology Unit, Oxon, England
OSTI ID:
5004549
Journal Information:
Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 7; ISSN IOBPD
Country of Publication:
United States
Language:
English

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Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
CONNECTIVE TISSUE CELLS
DRUGS
EFFICIENCY
FIBROBLASTS
HAMSTERS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IN VITRO
MAMMALS
MISONIDAZOLE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RODENTS
SOMATIC CELLS
TEMPERATURE DEPENDENCE
VERTEBRATES