PMID: 9416790Jan 7, 1998Paper

Oral platinum analogue JM216, a radiosensitizer in oxic murine cells

International Journal of Radiation Biology
P J van de VaartA C Begg

Abstract

This study was designed to compare radiosensitization by the oral platinum compound JM216 with cisplatin. RIF1 mouse tumour cells were treated at various doses and at various exposure times with JM216 and irradiated 15 min before the end of drug exposure. The fraction of cells surviving treatment was assessed by colony formation. Results were compared with those for equivalent treatments with cisplatin. JM216 alone showed exponential killing of RIF1 cells, being approximately three times less efficient than cisplatin on a molar basis. For radiosensitization studies, drug doses used gave approximately 50 or 90% cell killing alone. No radiosensitization was seen after 2-h drug exposures, but significant radiosensitization occurred after 1- and 0.5-h exposures (shorter times required proportionally higher drug doses, giving equivalent drug kill). The enhancement ratio and time dependence were similar for the two platinum compounds, reaching 1.5 at the highest concentrations tested. Drug DNA adduct formation was assessed using immunocytochemistry with the NKI-A59 antiserum raised to cisplatin-DNA adducts. The antiserum was shown to recognize JM216-DNA adducts in a dose-dependent manner and maximum nuclear staining was found to be c...Continue Reading

References

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