title: Low-dose radiation stimulates the proliferation of normal human lung fibroblasts via a transient activation of Raf and Akt.
abstract: The biological effects of low-dose radiation have been investigated and debated for more than a century, but its cellular effects and regulatory mechanisms remain poorly understood. This study shows the human cellular responses to low-dose radiation in CCD-18 Lu cells, which are derived from normal human lung fibroblasts. We examined a colony-forming assay for cell survival by ionizing radiation. Live cell counting and cell cycle analysis were measured for cell proliferation and cell cycle progression following low-dose irradiation. We examined Raf and Akt phosphorylation to determine the proliferation mechanism resulting from low-dose radiation. We also observed that p53 and p21 were related to cell cycle response. We found that 0.05 Gy of ionizing radiation enhanced cell proliferation and did not change the progression of the cell cycle. In addition, 0.05 Gy of ionizing radiation transiently activated Raf and Akt, but did not change phospho-p53, p53 and p21 in CCD-18 Lu cells. However, 2 Gy of ionizing radiation induced cell cycle arrest, phosphorylation of p53, and expression of p53 and p21. The phosphorylation of Raf and Akt proteins induced by 0.05 Gy of ionizing radiation was abolished by pre-treatment with an EGFR inhibitor, AG1478, or a PI3k inhibitor, LY294002. Cell proliferation stimulated by 0.05 Gy of ionizing radiation was blocked by the suppression of Raf and Akt phosphorylation with these inhibitors. These results suggest that 0.05 Gy of ionizing radiation stimulates cell proliferation through the transient activation of Raf and Akt in CCD-18 Lu cells.
authors.affiliation: Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., Seoul 132-703, Korea.
authors.forename: Cha Soon
authors.initials: CS
authors.lastname: Kim
authors.forename: Jin Kyoung
authors.initials: JK
authors.lastname: Kim
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Nam
authors.forename: Kwang Hee
authors.initials: KH
authors.lastname: Yang
authors.forename: Meeseon
authors.initials: M
authors.lastname: Jeong
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Chong Soon
authors.initials: CS
authors.lastname: Kim
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Jin
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
mesh_terms: D049109:Cell Proliferation / Q000528:radiation effects; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D008168:Lung / Q000166:cytology; D009025:Morpholines / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism / Q000528:radiation effects*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism / Q000528:radiation effects*; D011799:Quinazolines; D015398:Signal Transduction / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology; D054462:p21-Activated Kinases / Q000096:biosynthesis
chemical_list: D002867:Chromones; D009025:Morpholines; D011799:Quinazolines; D016159:Tumor Suppressor Protein p53; D020032:Tyrphostins; C101044:RTKI cpd; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf; D054462:p21-Activated Kinases