DNA damage responses in cell cycle G2 phase and mitosis--tracking and targeting.
BACKGROUND
In order to determine temporal responses of cell cycle populations to DNA damage, a rational combination of cell cycle analyses is critical. Moreover, the targeting of cell cycle checkpoint responses may modify the cytotoxic effect of DNA damage.


METHODS
The characteristics of cell cycle populations (DNA content, cell cycle transitioning of S phase cells and size of mitotic cell fraction within the total G2/M phase population) in HeLa cells exposed to ionizing radiation were analyzed using three individual flow cytometry-based assays. The potential radiosensitization from inhibiting DNA damage responses was assessed by the colony formation assay.


RESULTS
Irradiation resulted in an initial accumulation of S phase cells in G2 phase, from which the arrested cells were subsequently released to enter mitosis. Upon drug inhibition of G2 checkpoint signaling or mitotic progression, the cytotoxic effect of ionizing radiation on the HeLa cells was amplified.


CONCLUSIONS
DNA damage-induced cell cycle responses, analyzed by selected cytometry assays and modified by specific targeting, might contribute to an understanding of how to improve radiotherapy outcome.
Ree
Anne Hansen
AH
Department of Tumor Biology, The Norwegian Radium Hospital, 0310 Oslo, Norway. a.h.ree@medisin.uio.no
Stokke
Trond
T
Bratland
Ase
A
Patzke
Sebastian
S
Nome
Ragnhild V
RV
Folkvord
Sigurd
S
Meza-Zepeda
Leonardo A
LA
Flatmark
Kjersti
K
Fodstad
Oystein
O
Andersson
Yvonne
Y
D002455:Cell Division / Q000235:genetics / Q000528:radiation effects; D048708:Cell Growth Processes / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage / Q000502:physiology*; D005434:Flow Cytometry; D016195:G2 Phase / Q000235:genetics* / Q000528:radiation effects; D018390:Gene Targeting; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000235:genetics* / Q000528:radiation effects