Hypoxic cell sensitization to radiation damage by a new radiosensitizer: cis-dichloro-bis(1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole-N3)platinum(II) (flap).
A new, stable platinum coordination complex (FLAP) containing the 5-nitroimidazole, metronidazole, has been prepared and characterized. The square-planar platinum(II) complex has two metronidazole molecules and two chlorine atoms in the cis configuration. The properties of FLAP differ significantly from metronidazole alone or other platinum complexes tested in the same system. It has a low toxicity towards Chinese hamster ovary cells and is a very effective radiosensitizer toward hypoxic cells in vitro: a one-h pretreatment with a non-toxic dose of 50 microM gave an enhancement ratio of 2.4. No potentiation of aerated cells to X-irradiation damage was observed after a similar schedule of pretreatment at the higher dose of 100 microM FLAP.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005260:Female; D008795:Metronidazole / Q000031:analogs & derivatives*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010053:Ovary / Q000166:cytology; D010100:Oxygen; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D009944:Organoplatinum Compounds; D011838:Radiation-Sensitizing Agents; D008795:Metronidazole; C023359:iproplatin; C036789:dichlorobis(1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole)platinum (II); D002945:Cisplatin; D010100:Oxygen