Radiopotentiation by the oral platinum agent, JM216: Role of repair inhibition

George P. Amorino, Michael L. Freeman, David P. Carbone, David E. Lebwohl, Hak Choy

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Purpose: To test for in vitro radiopotentiation by the orally- administered platinum (IV) complex, JM216; to compare these results to cisplatin and carboplatin; and to investigate whether the mechanism of radiopotentiation involves repair inhibition of radiation-induced DNA damage. Methods and Materials: H460 human lung carcinoma cells were incubated with the drugs for 1 h at 37°C irradiated at room temperature, and returned to 37°C for 20 min. Cells were then rinsed and colony forming ability was assessed. Wild-type V79 Chinese hamster cells and radiosensitive, DNA repair- deficient mutant cell (XR-V15B) were also studied along with H460 cells, Ku86 cDNA, which encodes part of a protein involved in DNA repair, was transfected into XR-V15B cells as previously described. The effect of JM216 on sublethal damage repair (SLDR) was also assessed using split-dose recovery. Results: Using equally cytotoxic doses of JM216, cisplatin, and carboplatin, the radiation dose enhancement ratios (DER) were 1.39, 1.31, and 1.20, respectively; the DER with 20 μM JM216 was 1.57. JM216 (20 μM) did not significantly change the final slope of radiation survival curves, but greatly reduced the survival curve shoulder. V79 cells also showed radioenhancement using 20 μM JM216, but no enhancement occurred using XR- V15B cells. Transfection of Ku86 cDNA into XR-V15B cells restored radiopotentiation by JM216 to wild-type V79 levels. In addition, 20 μM JM216 completely inhibited sublethal damage repair in H460 cells. Conclusion: Our results show that JM216 can potentiate the effects of radiation in human lung cancer cells, an that the mechanism of this effect is probably inhibition of DNA repair by JM216.

Original languageEnglish (US)
Pages (from-to)399-405
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume44
Issue number2
DOIs
StatePublished - May 1 1999

Keywords

  • Cisplatin
  • H460
  • JM216
  • Ku
  • Lung cancer
  • Radiation
  • Repair inhibition
  • XR-V15B

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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