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Radiopotentiation by the oral platinum agent, JM216: role of repair inhibition by George P Amorino; Michael L Freeman; David P Carbone; David E Lebwohl; Hak Choy is a Medicine article available to read on EtoBox.

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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 cells (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 M JM216 was 1.57. JM216 (20 M) did not significantly change the final slope of radiation survival curves, but greatly reduced the survival cur

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Author

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

Publisher

Elsevier Science; Elsevier ; Elsevier BV (ISSN 0360-3016)

Published

1999

Language

EN

Field

Medicine (Health Sciences)