Correlations between radiation-induced double strand breaks and cell cycle checkpoints in X-irradiated NIH/3T3 fibroblasts.
BACKGROUND
To better understand the relationship between the formation of radiation-induced DNA double strand breaks (DSB) and cell cycle checkpoint activation, studies were conducted in the NIH/3T3 fibroblast cell line in order to establish correlations between the temporal appearance of gamma-H2AX foci (a DSB) and the expression of the cell cycle regulatory proteins, the cyclins, and their cyclin kinase inhibitor, p21.


METHODS
Immunocytochemistry was used to determine the expression of cyclin E, A, B1, p21, and the generation of DSB in NIH/3T3 cells exposed to 2 or 4 Gy X-irradiation.


CONCLUSIONS
The data suggest that the G1/S- and S-phase delay (cyclin E and cyclin A protein levels) are dependent on the dose of radiation while the G2/M (cyclin B1 protein levels) delay is dependent on the quantity of DSB sustained by the irradiated cell.
Cariveaua
Mickael J
MJ
Department of Physics, East Carolina University, Greenville, North Carolina, USA. cariveau@sri.org
Kalmus
Gerhard W
GW
Johnke
Roberta M
RM
Allison
Ron R
RR
Evans
Mark
M
Holbert
Donald
D
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects*; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D006657:Histones / Q000378:metabolism; D007124:Immunoenzyme Techniques; D051379:Mice; D041681:NIH 3T3 Cells; D014965:X-Rays
C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; C468783:H2AX protein, human; D006657:Histones