Relationships between EGFR-initiated signalling, DNA double-strand break rejoining and survival in X-irradiated human glioma M059 cells

• Autorzy: Grądzka I. , Buraczewska I. , Szumiel I.
• Języki publikacji: EN

Abstrakty

EN

The aim of this study was to investigate the effect of signalling inhibition on survival and double-strand break (DSB) rejoining in cells differing in sensitivity to inhibitors, X-rays and bleomycin. Human glioma M059 cells, K (relatively radioresistant) and J (radiosensitive, defective in DSB rejoining for lack of DNA-dependent protein kinase catalytic subunit, DNA-PKcs) were pretreated with signalling inhibitors: tyrphostin AG 1478, specific for epidermalgrowth- factor-receptor (EGFR) kinase or PD 98059, specific for kinase MEK 1/2 (mitogen-activated, extracellular signal-activated kinases 1 and 2). Subsequently, the cells were X-irradiated or treated with bleomycin. Cell survival was determined by clonogenicity test. DSB rejoining was monitored with the use of pulsed-field gel electrophoresis (PFGE). We found that in X-irradiated M059 K cells EGFR kinase activity was necessary for efficient DSB rejoining and the kinase inhibitor, tyrphostin AG 1478, acted as radiosensitizer in the dose range that reduced cell survival to 0.7-0.8. Inhibition of EGFR kinase, however, did not decrease survival or affect DSB rejoining in DNA-PKcs-deficient M059 J cells. These results indicated that the decrease in cell survival was due to a disturbed DSB rejoining by the DNA-PK dependent system. In contrast, inhibition of MEK 1/2 kinase on EGFR downstream signalling pathway by PD 98059 did not affect DSB rejoining in either cell line and exerted a radioprotective effect.

Słowa kluczowe

EN

human glioma M059 K and J cells; DNA-dependent protein kinase (DNA-PK); radiosensitivity; DNA double-strand break (DSB) rejoining; epidermal-growth-factor-receptor (EGFR); signalling inhibitors: tyrphostin

• Wydawca: Institute of Nuclear Chemistry and Technology
• Czasopismo: Nukleonika
• Rocznik: 2008
• Tom: Vol. 53, No. 2
• Strony: 37--44
• Opis fizyczny: Bibliogr. 33 poz., rys.

Twórcy

autor

Grądzka I.

autor

Buraczewska I.

autor

Szumiel I.

• Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland, Tel.: [phone], Fax: [phone],

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