title: Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation.
abstract: Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understanding the radiobiological changes observed in bystander cells in response to the signals from irradiated cells in a normal cell population with implications to radiation risk assessment. However, reports on RIBE with relevance to cancer radiotherapy especially investigating the bidirectional and criss-cross bystander communications between cancer and normal cells are limited. Hence, in present study employing co-culture approach, we have investigated the bystander cross-talk between lung cancer (A549) and normal (WI38) cells after proton-microbeam irradiation using γ-H2AX foci fluorescence as a measure of DNA double-strand breaks (DSBs). We observed that in A549-A549 co-cultures, irradiated A549 cells exert damaging effects in bystander A549 cells, which were found to be mediated through gap junctional intercellular communication (GJIC). However, in A549-WI38 co-cultures, irradiated A549 did not affect bystander WI38 cells. Rather, bystander WI38 cells induced inverse protective signalling (rescue effect) in irradiated A549 cells, which was independent of GJIC. On the other hand, in response to irradiated WI38 cells neither of the bystander cells (A549 or WI38) showed significant increase in γ-H2AX foci. The observed bystander signalling between tumour and normal cells may have potential implications in therapeutic outcome of cancer radiotherapy.
authors.affiliation: Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
authors.forename: Sejal
authors.initials: S
authors.lastname: Desai
authors.affiliation: Radiation System and Engineering Section, Department of Technical Support and Development, Research, Development and Support Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Alisa
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Radiation System and Engineering Section, Department of Technical Support and Development, Research, Development and Support Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Konishi
authors.affiliation: Radiation System and Engineering Section, Department of Technical Support and Development, Research, Development and Support Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Oikawa
authors.affiliation: Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India. Electronic address: badrinarain@yahoo.co.in.
authors.forename: Badri N
authors.initials: BN
authors.lastname: Pandey
mesh_terms: D024201:Bystander Effect / Q000528:radiation effects*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004273:DNA, Neoplasm / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D009363:Neoplasm Proteins / Q000378:metabolism; D011522:Protons
chemical_list: D004273:DNA, Neoplasm; C468783:H2AX protein, human; D006657:Histones; D009363:Neoplasm Proteins; D011522:Protons
keywords: Bystander cross-talk; DNA double-strand breaks; Gap junctional intercellular communication; Human lung cancer and normal fibroblast cells; Proton microbeam; γ-H2AX