Radiosensitization of mammalian cells by transition metal complexes containing nitroimidazole ligands.
Various transition metal complexes containing nitroimidazoles as ligands have been shown to act as radiosensitizers of hypoxic cells in vitro. Sensitization by cis-Pt(II)Cl2 (nitroimidazole)2 complexes is no greater than that which can be demonstrated by the free nitroimidazole ligand alone. These results differ from those previously described for the compound FLAP where an ER of 2.4 was obtained at a concentration of 50 microM. We report that, even using the same treatment technique, the maximum ER that can be achieved is 1.2. Further, the sensitizing efficiency of FLAP cannot be improved when cells are kept in contact with the compound for 12 hours in air prior to deoxygenation and irradiation. In contrast, Rh(II) complexes show much greater sensitization than can be obtained with the free ligand and these compounds are in turn more efficient sensitizers than the comparable Pt(II) complexes.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005260:Female; D008795:Metronidazole / Q000031:analogs & derivatives*; D009593:Nitroimidazoles / Q000494:pharmacology*; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010053:Ovary; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012238:Rhodium / Q000494:pharmacology*
D009593:Nitroimidazoles; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; D011838:Radiation-Sensitizing Agents; D008795:Metronidazole; C036789:dichlorobis(1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole)platinum (II); C042595:RSU 1113; C042594:RSU 1130; D012238:Rhodium