Evaluation of Thermal Cisplatin Sensitization in Chicken DT40 Cells, Normal and Deficient, in DNA Homologous and Nonhomologous Endjoining Repair
G. P. Raaphorst,
J- Maude Leblanc.
Hyperthermia has been shown in many studies to be a strong sensitizer for cisplatin treatment and this sensitization may be in part due to the inhibition of DNA repair processes. We have set out to test this in cells with specific gene knockouts for known repair processes. The chicken DT40 cell system was used with a parental line (DT40) and knockouts of homologous recombination (HR) repair DT40Rad54, nonhomologous recombination endjoining (NHEJ) repair (DT40Ku70) and a double knockout mutant DT40Ku70Rad54. The results show that thermal cisplatin sensitization was achieved in all cell lines when hyperthermia at 45°C for 1.5h was given before cisplatin treatment and 42°C hyperthermia was given concurrently with cisplatin treatment. The data show that inhibition of the HR repair system did not significantly affect sensitization, while inhibition of NHEJ reduced thermal sensitization at low cisplatin doses and short treatments and for concurrent treatments. These data indicate that there may be a partial involvement of NHEJ in thermal cisplatin sensitization under specific treatment conditions.
Keywords: cisplatin, hyperthermia, homologous recombination, nhej
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