Platinum complexes with one radiosensitizing ligand (PtCl2(NH3) (sensitizer)): radiosensitization and toxicity studies in vitro
Complexes of general formula (PtCl2(NH3)L) with one radiosensitizing ligand per platinum are compared with ligand L alone, complexes with two radiosensitizers per platinum (PtCl2L2), and their analogs with NH3 ligands, with respect to radiosensitizing properties and toxicity in CHO cells. Radiosensitizing ligands, L, were misonidazole, metronidazole, 4(5)-nitroimidazole, and 2-amino-5-nitrothiazole, and the ammine analogs were cis- and trans-DDP (diamminedichloroplatinum(II)) and the monoammine, K(PtCl3(NH3)). Results are related to a previous study on plasmid DNA binding by these series. The toxicity of the mono series (PtCl2(NH3)L), attributable to DNA binding, is much higher than the corresponding bis complexes, (PtCl2L2). For L = misonidazole, toxicity is similar to the monoammine, but higher in hypoxic than in aerobic cells. trans-(PtCl2(NH3)-(misonidazole)) is more toxic than the cis isomer. Except for L = 4(5)-nitroimidazole, the complexes (PtCl2(NH3)L) are more toxic than L in air and hypoxia. Hypoxic radiosensitization by the mono complexes is comparable to the monoammine and is not better than free sensitizers, again except for L = 4(5)-nitroimidazole. Significantly lower sensitization is observed in oxic cells. The bis complexes (PtCl2L2), which do not bind to DNA as well as the mono complexes, are less effective radiosensitizers and less toxic than the (PtCl2(NH3)L) series.
- Research Organization:
- B. C. Cancer Research Centre, Vancouver
- OSTI ID:
- 5650833
- Journal Information:
- Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 112:2; ISSN RAREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANIMAL CELLS
ANTINEOPLASTIC DRUGS
AZOLES
CHO CELLS
COMPARATIVE EVALUATIONS
COMPLEXES
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMIDAZOLES
IN VITRO
METRONIDAZOLE
MISONIDAZOLE
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PLATINUM COMPLEXES
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
THIAZOLES
TOXICITY
TRANSITION ELEMENT COMPLEXES