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      Assessing Toxicity and Nuclear and Mitochondrial DNA Damage Caused by Exposure of Mammalian Cells to Lunar Regolith Simulants

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          Abstract

          Previous missions to the lunar surface implicated potential dangers of lunar soil. In future explorations, astronauts may spend weeks or months on the Moon, increasing the risk of inhaling lunar dust. In an effort to understand the biological impact of lunar regolith, cell cultures derived from lung or neuronal cells were challenged with lunar soil simulants to assess cell survival and genotoxicity. Lunar soil simulants were capable of causing cell death and DNA damage in neuronal and lung cell lines, and freshly crushed lunar soil simulants were more effective at causing cell death and DNA damage than were simulants as received from the supplier. The ability of the simulants to generate reactive oxygen species in aqueous suspensions was not correlated with their cytotoxic or genotoxic affects. Furthermore, the cytotoxicity was not correlated with the accumulation of detectable DNA lesions. These results determine that lunar soil simulants are, with variable activity, cytotoxic and genotoxic to both neuronal and lung‐derived cells in culture.

          Key Points

          • Lunar soil may pose a health risk when inhaled by astronauts

          • Lunar soil simulants have cytotoxic and genotoxic effects on neuronal and lung epithelial cells

          • Cytotoxicity of the soils was not correlated with the DNA damage they caused in neuronal and lung cells

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          Most cited references39

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          DNA damage and the balance between survival and death in cancer biology.

          DNA is vulnerable to damage resulting from endogenous metabolites, environmental and dietary carcinogens, some anti-inflammatory drugs, and genotoxic cancer therapeutics. Cells respond to DNA damage by activating complex signalling networks that decide cell fate, promoting not only DNA repair and survival but also cell death. The decision between cell survival and death following DNA damage rests on factors that are involved in DNA damage recognition, and DNA repair and damage tolerance, as well as on factors involved in the activation of apoptosis, necrosis, autophagy and senescence. The pathways that dictate cell fate are entwined and have key roles in cancer initiation and progression. Furthermore, they determine the outcome of cancer therapy with genotoxic drugs. Understanding the molecular basis of these pathways is important not only for gaining insight into carcinogenesis, but also in promoting successful cancer therapy. In this Review, we describe key decision-making nodes in the complex interplay between cell survival and death following DNA damage.
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            Nanoparticle Uptake: The Phagocyte Problem.

            Phagocytes are key cellular participants determining important aspects of host exposure to nanomaterials, initiating clearance, biodistribution and the tenuous balance between host tolerance and adverse nanotoxicity. Macrophages in particular are believed to be among the first and primary cell types that process nanoparticles, mediating host inflammatory and immunological biological responses. These processes occur ubiquitously throughout tissues where nanomaterials are present, including the host mononuclear phagocytic system (MPS) residents in dedicated host filtration organs (i.e., liver, kidney spleen, and lung). Thus, to understand nanomaterials exposure risks it is critical to understand how nanomaterials are recognized, internalized, trafficked and distributed within diverse types of host macrophages and how possible cell-based reactions resulting from nanomaterial exposures further inflammatory host responses in vivo. This review focuses on describing macrophage-based initiation of downstream hallmark immunological and inflammatory processes resulting from phagocyte exposure to and internalization of nanomaterials.
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              Mechanisms of nanotoxicity: Generation of reactive oxygen species⋆

              Nanotechnology is a rapidly developing field in the 21 st century, and the commercial use of nanomaterials for novel applications is increasing exponentially. To date, the scientific basis for the cytotoxicity and genotoxicity of most manufactured nanomaterials are not understood. The mechanisms underlying the toxicity of nanomaterials have recently been studied intensively. An important mechanism of nanotoxicity is the generation of reactive oxygen species (ROS). Overproduction of ROS can induce oxidative stress, resulting in cells failing to maintain normal physiological redox-regulated functions. This in turn leads to DNA damage, unregulated cell signaling, change in cell motility, cytotoxicity, apoptosis, and cancer initiation. There are critical determinants that can affect the generation of ROS. These critical determinants, discussed briefly here, include: size, shape, particle surface, surface positive charges, surface-containing groups, particle dissolution, metal ion release from nanometals and nanometal oxides, UV light activation, aggregation, mode of interaction with cells, inflammation, and pH of the medium.
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                Author and article information

                Contributors
                bruce.demple@stonybrook.edu
                Journal
                Geohealth
                Geohealth
                10.1002/(ISSN)2471-1403
                GH2
                GeoHealth
                John Wiley and Sons Inc. (Hoboken )
                2471-1403
                26 April 2018
                April 2018
                : 2
                : 4 ( doiID: 10.1002/gh2.v2.4 )
                : 139-148
                Affiliations
                [ 1 ] Department of Pharmacological Sciences Stony Brook University School of Medicine Stony Brook NY USA
                [ 2 ] Program in Genetics Stony Brook University Stony Brook NY USA
                [ 3 ] Department of Geosciences Stony Brook University Stony Brook NY USA
                Author notes
                [*] [* ] Correspondence to: B. Demple,

                bruce.demple@ 123456stonybrook.edu

                Author information
                http://orcid.org/0000-0001-6411-1162
                http://orcid.org/0000-0002-5857-8652
                http://orcid.org/0000-0001-9917-7479
                Article
                GH262 2017GH000125
                10.1002/2017GH000125
                7007071
                32159013
                c740b577-eba7-4f03-8844-294e0f3084d5
                ©2018. The Authors.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 11 December 2017
                : 20 March 2018
                : 03 April 2018
                Page count
                Figures: 5, Tables: 2, Pages: 10, Words: 4894
                Funding
                Funded by: NASA , open-funder-registry 10.13039/100000104;
                Award ID: NNA‐14AB04A
                Categories
                Science and Exploration of the Moon, Near‐Earth Asteroids, and the Moons of Mars
                Biogeosciences
                Soils/Pedology
                Hydrology
                Soils
                Research Article
                Research Articles
                Custom metadata
                2.0
                April 2018
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.4 mode:remove_FC converted:09.01.2020

                particle toxicity,lunar soil,dna integrity,neuronal differentiation,space weathering

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