Low-dose of ionizing radiation enhances cell proliferation via transient ERK1/2 and p38 activation in normal human lung fibroblasts.
This study shows the human cellular responses and the mechanism of low-dose ionizing radiation in CCD 18 Lu cells, which are derived from normal human lung fibroblasts. Cell proliferation and viability assay were measured for the cells following gamma-irradiation using trypan blue, BrdU incorporation, and Wst-1 assay. We also examined genotoxicity using a micronuclei formation assay. The activation of the MAPKs pathway was determined by Western blot analysis, and the siRNA system was used to inhibit the expression of ERK1/2 and p38. We found that 0.05 Gy of ionizing radiation stimulated cell proliferation and did not change Micronuclei frequencies. In addition, 0.05 Gy of ionizing radiation activated ERK1/2 and p38, but did not activate JNK1/2 in cells. A specific ERK1/2 inhibitor, U0126, decreased the phosphorylation of ERK1/2 proteins induced by 0.05 Gy of ionizing radiation, and a similar suppressive effect was observed with a p38 inhibitor, PD169316. Suppression of ERK1/2 and p38 phosphorylation with these inhibitors decreased cell proliferation, which was stimulated by 0.05 Gy of ionizing radiation. Furthermore, downregulation of ERK1/2 and p38 expression using siRNA blocked the cell proliferation that had been increased by 0.05 Gy of ionizing radiation. These results suggest that 0.05 Gy of ionizing radiation enhances cell proliferation through the activation of ERK1/2 and p38 in normal human lung fibroblasts.
Radiation Health Research Institute, Korea Hydro & Nuclear Power Co., LTD, Seoul, Republic of Korea.
Cha Soon
CS
Kim
Jin-Mo
JM
Kim
Seon Young
SY
Nam
Kwang Hee
KH
Yang
Meeseon
M
Jeong
Hee Sun
HS
Kim
Young-Khi
YK
Lim
Chong Soon
CS
Kim
Young-Woo
YW
Jin
Joon
J
Kim
D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation / Q000528:radiation effects; D005347:Fibroblasts / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D020935:MAP Kinase Signaling System / Q000502:physiology* / Q000528:radiation effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D011829:Radiation Dosage; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases