Radiosensitization of CHO cells by two novel rhodium complexes under oxic and hypoxic conditions.
BACKGROUND
Tumour hypoxia severely limits the success of radiotherapy. Radiosensitization of hypoxic tumour cells by drugs is thus an important clinical issue.


METHODS
Two novel ferrocene-containing beta-diketonato complexes of the transition metals rhodium and iridium were examined for their cytotoxic activity against Chinese hamster ovary (CHO) cells by MTT and clonogenic assays. The same complexes were also tested for their capacity to sensitize hypoxic CHO cells against 8 MeV photons.


RESULTS
The IC50 for [Rh(fcta)(cod)] (I) and [Rh (fctca)(cod)] (II), where (fctfa) = ferrocenoylacetonato-4,4,4-trifluoro and (fctca) = ferrocenoyl-4,4,4-trichloro- and (cod) = 1,5-cyclooctadiene, were found to be 1.38 microM and 4.18 microM, respectively, closely resembling that of cisplatin which was found to be 1.21 microM. The rhodium (I) complex was identified as an effective anoxic radiosensitizer showing a dose-modifying factor (DMF) of 1.93 +/- 0.02, resembling cisplatin where the DMF was found to be 1.99 +/- 0.02. Small DMF's in the range of 1.10 were also found for cisplatin and the rhodium (I) complex under aerobic conditions, but these were not statistically significant. The DMF for the iridium complex was small and found to be 1.06 +/- 0.04.


CONCLUSIONS
The cytotoxicity and radiosensitizing properties of the rhodium (I) complex are very similar to cisplatin and show considerable potential for clinical application.
Falzone
Nadia
N
Department of Biomedical Sciences, Tswhane University of Technology, Pretoria, South Africa.
Böhm
Lothar
L
Swarts
Jannie C
JC
Van Rensburg
Constance E J
CE
D000818:Animals; D016466:CHO Cells; D015687:Cell Hypoxia; D006224:Cricetinae; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology; D000075163:Metallocenes; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D012238:Rhodium / Q000737:chemistry / Q000494:pharmacology*
D005296:Ferrous Compounds; D000075163:Metallocenes; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C487803:ferrocenoyltrifluoroacetone; C508289:rhodiium ferrocenoyl-4,4,4-trichloro-1,5-cyclooctadiene; C508288:rhodium-ferrocenoylacetonato-4,4,4-trifluoro-1,5-cyclooctadiene; D012238:Rhodium; C004998:ferrocene