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.
Skov
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Medical Biophysics Unit, B. C. Cancer Research Centre, Vancouver, Canada.
Farrell
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Adomat
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D000818:Animals; D002945:Cisplatin / Q000633:toxicity; D006224:Cricetinae; D066298:In Vitro Techniques; D008795:Metronidazole / Q000633:toxicity; D008920:Misonidazole / Q000633:toxicity; D009593:Nitroimidazoles / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000633:toxicity; D013844:Thiazoles / Q000633:toxicity
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D013844:Thiazoles; D008795:Metronidazole; C034870:2-amino-5-nitrothiazole; D008920:Misonidazole; D002945:Cisplatin; C052587:4-nitroimidazole