New ruthenium radiosensitizer: RuCl2(DMSO)2(4-nitroimidazole)2
Journal Article
·
· Int. J. Radiat. Oncol., Biol. Phys.; (United States)
Earlier studies on Ru complexes, such as, cis-RuCl2(DMSO)4, as antineoplastic agents, have suggested a DNA binding mechanism similar to that of the clinically successful platinum complex, cis-diammine(dichloro)platinum(II), (cis-DDP). As part of our study on metal-radiosensitizer complexes, cis-RuCl2(DMSO)4 is used as a precursor for synthesis of Ru(II)-nitroimidazole complexes. These complexes were identified and characterized and their toxicity and radiosensitizing abilities were examined in vitro. In the series of Ru(II)-nitroimidazole complexes synthesized, RuCl2(DMSO)2(4-nitroimidazole)2, Ru-(4-nitro), was the most effective radiosensitizer. At 200 microM, Ru-(4-nitro) produced a sensitizer enhancement ratio (SER) of 1.6 in hypoxic Chinese hamster ovary (CHO) cells, but did not sensitize oxic CHO cells. Other Ru-nitroimidazole complexes gave SER values of 1.2-1.4 at 200 microM. These Ru(II)-nitroimidazole complexes also showed lower toxicity than the free nitroimidazoles alone at equimolar concentration. The enhanced radiosensitizing effect of Ru-(4-nitro) may be due to the metal's ability to target the sensitizer to DNA, or may be related to changes in reduction potential: from -685 mV for the free ligand to -355 mV and -615 mV for the complex. This complex did not deplete non-protein sulfhydryls (NPSH) at the time intervals and concentrations used. DNA binding was studied using inhibition of restriction enzyme activity on plasmid DNA.
- Research Organization:
- B.C. Cancer Research Centre, Vancouver
- OSTI ID:
- 5072205
- 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
560121* -- Radiation Effects on Cells-- External Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
AZOLES
CHO CELLS
COMPLEXES
DNA
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOMETALLIC COMPOUNDS
RADIOSENSITIVITY EFFECTS
RUTHENIUM COMPLEXES
TOXICITY
TRANSITION ELEMENT COMPLEXES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
AZOLES
CHO CELLS
COMPLEXES
DNA
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOMETALLIC COMPOUNDS
RADIOSENSITIVITY EFFECTS
RUTHENIUM COMPLEXES
TOXICITY
TRANSITION ELEMENT COMPLEXES