Low-Dose Radiation Induces Cell Proliferation in Human Embryonic Lung Fibroblasts but not in Lung Cancer Cells

Abstract

Hormesis and adaptive responses are 2 important biological effects of low-dose ionizing radiation (LDR). In normal tissue, LDR induces hormesis as evinced by increased cell proliferation; however, whether LDR also increases tumor cell proliferation needs to be investigated. In this study, cell proliferation was assayed by total cell numbers and the Cell Counting Kit 8 assay. Mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3′ -kinase(PI3K)-Akt (PI3K/AKT) phosphorylation were determined by Western blot analysis. Human embryonic lung fibroblast 2BS and lung cancer NCI-H446 cell lines were irradiated with LDR at different doses (20-100 mGy). In response to 20 to 75 mGy X-rays, cell proliferation was significantly increased in 2BS but not in NCI-H446 cells. In 2BS cells, LDR at 20 to 75 mGy also stimulated phosphorylation of MAPK/ERK pathway proteins including ERK, MEK, and Raf and of the PI3K/AKT pathway protein AKT. To test whether ERK1/2 and AKT pathway activation was involved in the stimulation of cell proliferation in 2BS cells, the MAPK/ERK and PI3K/AKT pathways were inhibited using their specific inhibitors, U0126 and LY294002. U0126 decreased the phosphorylation of ERK1/2, and LY294002 decreased the phosphorylation of AKT; each could significantly inhibit LDR-induced 2BS cell proliferation. However, LDR did not stimulate these kinases, and kinase inhibitors also did not affect cell proliferation in the NCI-H446 cells. These results suggest that LDR stimulates cell proliferation via the activation of both MAPK/ERK and PI3K/AKT signaling pathways in 2BS but not in NCI-H446 cells. This finding implies the potential for applying LDR to protect normal tissues from radiotherapy without diminishing the efficacy of tumor therapy.

Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells

“…Indeed, H2AX can be phosphorylated during replication when errors, such as stalled replication forks, occur and this phosphorylation is ATR, but not ATM, dependent [ 47 , 48 ]. These errors may be a result of an increased generation of reactive oxygen and nitrogen species characteristic of the S-phase metabo-lism and low-dose radiation can stimulate proliferation [ 49 – 51 ]. Unlike DNA double-strand breaks directly induced by radiation (or by water hydrolysis products upon irradiation), S-phase replication errors typically result in single-stranded DNA lesions and single-ended DNA double-strand breaks that trigger activation of and are processed by the ATR kinase via homologous recombination only [ 42 , 52 ].…”

125I Seeds Radiation Induces Paraptosis-Like Cell Death via PI3K/AKT Signaling Pathway in HCT116 Cells

“…Increased kinase activation is a common event in cancer cells after exposure to radiation [20–23]. We thus tested whether 125 I seeds radiation affected the protein expression of PI3K/AKT signaling pathway.…”

Ocena wpływu dawki i mocy promieniowania jonizującego na komórki raka piersi. The assessment of the effect of ionizing radiation dose and dose rate for breast cancer cells

“…Termin ten obejmuje stymulację każdego układu na ekspozycję niskich dawek dowolnego czynnika (29). Liang et al analizowali i porównywali wpływ LDR na komórki nowotworowe i prawidłowe (30). Fakt, że niska dawka może wywoływać hormezę w zdrowych komórkach może stanowić nowe podejście do zapewnienia pacjentom ekspozycji na LDR przed właściwą radioterapią.…”