title: Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.
abstract: The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types.
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, 400085, India. Electronic address: somnath@barc.gov.in.
authors.forename: Somnath
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
authors.forename: Anu
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
authors.forename: Malini
authors.initials: M
authors.lastname: Krishna
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism*; D024201:Bystander Effect; D045744:Cell Line, Tumor; D004249:DNA Damage; D005720:Gamma Rays; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008175:Lung Neoplasms / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000737:chemistry; D014162:Transfection; D020298:U937 Cells
chemical_list: C468783:H2AX protein, human; D006657:Histones; D034741:RNA, Small Interfering; C016658:phorbolol myristate acetate; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D013755:Tetradecanoylphorbol Acetate
keywords: ATM; Bystander effect; DNA damage response; H2AX