Cyclic hypoxia does not alter RAD51 expression or PARP inhibitor cell kill in tumor cells

Ramya Kumareswaran; Naz Chaudary; Karolina Jaluba; Alice Meng; Jenna Sykes; Asm Borhan; Richard P Hill; Robert G Bristow

doi:10.1016/j.radonc.2015.03.027

Cyclic hypoxia does not alter RAD51 expression or PARP inhibitor cell kill in tumor cells

Radiother Oncol. 2015 Sep;116(3):388-91. doi: 10.1016/j.radonc.2015.03.027. Epub 2015 Apr 2.

Authors

Ramya Kumareswaran¹, Naz Chaudary¹, Karolina Jaluba¹, Alice Meng¹, Jenna Sykes¹, Asm Borhan¹, Richard P Hill², Robert G Bristow³

Affiliations

¹ Ontario Cancer Institute, Princess Margaret Cancer Centre (University Health Network), Canada.
² Ontario Cancer Institute, Princess Margaret Cancer Centre (University Health Network), Canada; Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Canada.
³ Ontario Cancer Institute, Princess Margaret Cancer Centre (University Health Network), Canada; Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Canada. Electronic address: rob.bristow@rmp.uhn.on.ca.

PMID: 25842967
DOI: 10.1016/j.radonc.2015.03.027

Abstract

Solid tumors contain regions of chronic and cyclic hypoxia. Chronic hypoxia can downregulate RAD51 and sensitize cells to PARP inhibition. Herein, we show that RAD51 expression, cell survival and toxicity to PARP inhibition is not affected under cyclic hypoxic conditions. This suggests that PARP inhibition may be selectively toxic in tumor sub-regions associated with chronic hypoxia.

Keywords: Cyclic hypoxia; DNA repair; PARP inhibition; RAD51.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Blotting, Western
Cell Line, Tumor
Cell Survival
Cells, Cultured
Down-Regulation
Female
Humans
Hypoxia / metabolism*
Lung Neoplasms / metabolism*
Poly(ADP-ribose) Polymerase Inhibitors / metabolism*
Rad51 Recombinase / metabolism*
Uterine Cervical Neoplasms / metabolism*

Substances

Poly(ADP-ribose) Polymerase Inhibitors
Rad51 Recombinase