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      Effect of internal contamination with tritiated water on the neoplastic colonies in the lungs, innate anti-tumour reactions, cytokine profile, and haematopoietic system in radioresistant and radiosensitive mice

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          Abstract

          Tritium is a potentially significant source of internal radiation exposure which, at high levels, can be carcinogenic. We evaluated whether single intraperitoneal injection of BALB/c and C57BL/6 mice with tritiated water (HTO) leading to exposure to low (0.01 or 0.1 Gy) and intermediate (1.0 Gy) cumulative whole-body doses of β radiation is immunosuppressive, as judged by enhancement of artificial tumour metastases, functioning of NK lymphocytes and macrophages, circulating cytokine’s levels, and numbers of bone marrow, spleen, and peripheral blood cells. We demonstrate that internal contamination of radiosensitive BALB/c and radioresistant C57BL/6 mice with HTO at all the absorbed doses tested did not affect the development of neoplastic colonies in the lungs caused by intravenous injection of syngeneic cancer cells. However, internal exposure of BALB/c and C57BL/6 mice to 0.1 and 0.01 Gy of β radiation, respectively, up-regulated cytotoxic activity of and IFN-γ synthesis in NK lymphocytes and boosted macrophage secretion of nitric oxide. Internal contamination with HTO did not affect the serum levels of pro- (IL-1β, IL-2, IL-6, TNF-α,) and anti-inflammatory (IL-1Ra, IL-4, IL-10) cytokines. In addition, exposure of mice of both strains to low and intermediate doses from the tritium-emitted β-particles did not result in any significant changes in the numbers of bone marrow, spleen, and peripheral blood cells. Overall, our data indicate that internal tritium contamination of both radiosensitive and radioresistant mice leading to low and intermediate absorbed β-radiation doses is not immunosuppressive but may enhance some but not all components of anticancer immunity.

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          Most cited references43

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          Distinct role of macrophages in different tumor microenvironments.

          Macrophages are prominent in the stromal compartment of virtually all types of malignancy. These highly versatile cells respond to the presence of stimuli in different parts of tumors with the release of a distinct repertoire of growth factors, cytokines, chemokines, and enzymes that regulate tumor growth, angiogenesis, invasion, and/or metastasis. The distinct microenvironments where tumor-associated macrophages (TAM) act include areas of invasion where TAMs promote cancer cell motility, stromal and perivascular areas where TAMs promote metastasis, and avascular and perinecrotic areas where hypoxic TAMs stimulate angiogenesis. This review will discuss the evidence for differential regulation of TAMs in these microenvironments and provide an overview of current attempts to target or use TAMs for therapeutic purposes.
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            High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal.

            High-mobility group box 1 protein (HMGB1), which previously was thought to function only as a nuclear factor that enhances transcription, was recently discovered to be a crucial cytokine that mediates the response to infection, injury and inflammation. These observations have led to the emergence of a new field in immunology that is focused on understanding the mechanisms of HMGB1 release, its biological activities and its pathological effects in sepsis, arthritis, cancer and other diseases. Here, we discuss these features of HMGB1 and summarize recent advances that have led to the preclinical development of therapeutics that modulate HMGB1 release and activity.
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              Inside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox.

              Immune responses are initiated and perpetuated by molecules derived from microorganisms pathogen-associated molecular-pattern molecules or from the damage or death of host cells [damage-associated molecular-pattern (DAMP) molecules]. Many DAMPs are nuclear or cytosolic proteins with defined intracellular function that, when released outside the cell following tissue injury, move from a reducing to an oxidizing milieu resulting in their functional denaturation. Here, we discuss the consequences of DAMP oxidation on the outcome of acute inflammation. We also suggest that, outside the cell, DAMPs might adopt novel conformations or alter the redox of the extracellular environment to more closely mimic the internal one, thereby avoiding oxidation-mediated inactivation and promoting pathology. We propose that chronic inflammation associated with autoimmunity, chronic viral infection and cancer is probably mediated by persistent release and function of DAMPs, promoting and promoted by a disordered redox environment.
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                Author and article information

                Contributors
                +48 261816135 , enowosielska@wihe.waw.pl
                Journal
                Radiat Environ Biophys
                Radiat Environ Biophys
                Radiation and Environmental Biophysics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0301-634X
                1432-2099
                6 April 2018
                6 April 2018
                2018
                : 57
                : 3
                : 251-264
                Affiliations
                [1 ]ISNI 0000 0001 1371 5636, GRID grid.419840.0, Department of Radiobiology and Radiation Protection, , Military Institute of Hygiene and Epidemiology, ; 4 Kozielska St., 01-163 Warsaw, Poland
                [2 ]ISNI 0000 0001 1371 5636, GRID grid.419840.0, Department of Regenerative Medicine and Cell Biology, , Military Institute of Hygiene and Epidemiology, ; 4 Kozielska St., 01-163 Warsaw, Poland
                [3 ]ISNI 0000 0004 0367 7826, GRID grid.280401.f, Lovelace Respiratory Research Institute, ; 2425 Ridgecrest Drive SE, Albuquerque, 87108 NM USA
                Author information
                http://orcid.org/0000-0002-5533-4804
                Article
                739
                10.1007/s00411-018-0739-4
                6060768
                29626227
                7ace0666-9efa-4840-a3f9-99ea710287fc
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 22 January 2018
                : 21 March 2018
                Funding
                Funded by: Polish National Science Centre
                Award ID: DEC-2011/01/D/NZ7/05389
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2018

                Biophysics
                low-level radiation,tritiated water,artificial tumour colonies,nk cells,macrophages,cytokines

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