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Cancer / Oncology News

Sensing Of DNA-dsbs Under Continual Hypoxia

Main Category: Cancer / Oncology
Also Included In: Genetics;  Blood / Hematology;  Radiology / Nuclear Medicine
Article Date: 22 Sep 2008 - 4:00 PDT

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Intracellular hypoxia has been linked to genetic instability, tumour progression and poor prognosis. Little is known about the effect of hypoxia on DNA-dsb sensing and repair. We tested whether the sensing of DNA-dsbs and chromatin biology is decreased in cells irradiated under continual hypoxic or anoxic conditions. To test this hypothesis, we used normal diploid fibroblast strains, GM05757, synchronised in G0-G1 to preclude DNA replication as a source of DNA repair foci.

The cells were pre-treated with 0.2% O2 (hypoxia), 0.0% O2 (anoxia) or 21% O2 (normoxia) for 16 hours and then irradiated and kept under hypoxic/ anoxic/ normoxic conditions for another 24 hours.

The biomarkers gammaH2AX, MRE11, 53BP1, ATMser1981 and the MRN complexes were tracked using quantitative immunofluorescent microscopy to score intranuclear foci. We observed an expected 2 to 3 fold decrease in initial number of gammaH2AX ATMser1981 and 53BP1 foci at 30 minutes following 2 or 5 Gy post-IR under hypoxia and anoxia consistent with the OER. However, we observed an increase in the relative ATM-dependent residual foci at times between 4 and 24 hours post-IR under continual hypoxia. These were residual DNA-dsbs based on neutral COMET assays and were not associated with increased cell kill following clongenic assays, suggesting misrepair or repair can occur in such cells when releases into S and G2Mphases. We conclude that hypoxic cells have an altered ability during NHEJ to sense and repair DNA-dsbs and could serve as a potential factor in genetic instability and tumour progression.

Supported by a Terry Fox Hypoxia Project Program Grant and CCS Career Award to RGB.

Bristow Robert et al. Princess Margaret Hospital and University of Toronto, Toronto, Canada

About ESTRO 27

ESTRO 27
(September 14th to 18th, 2008) offered an outstanding scientific programme combining lectures from eminent invited speakers, proffered papers and poster discussions, teaching lectures on a wide range of topics including clinical issues, brachytherapy, radiobiology, physics and technology as well as debates on controversial topics and clinical case discussions, a special poster reception, poster discussion sessions and electronic poster viewing.

ESTRO 27 hosted the largest European exhibition in Radiotherapy with participation from all the leading manufacturers.

ESTRO 27

ESTRO (European Society for Therapeutic Radiology and Oncology)



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