Phospholipid surfactant adsorption by respirable quartz and in vitro expression of cytotoxicity and DNA damage

Liu, X; Keane, Michael; Harrison, Joel C.; Cilento, Eugene V.; Ong, T.; Wallace, W.E.

doi:10.1016/s0378-4274(98)00053-8

Cited by 24 publications

(27 citation statements)

References 9 publications

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“…In line with our findings with PVNO or lactate, others have demonstrated that genotoxic effects as measured by micronucleus formation in V79 cells (Liu et al, 1996) or as determined in rat macrophages using the comet assay (Liu et al, 1998) is largely affected if treated with surfactant/DPPC. Earlier, the same research group investigated the role of surfactant in the genotoxicity of DEP using the Salmonella mutagenicity test and the sister chromatid exchange (SCE) assay in V79 cells (Keane et al, 1991).…”

Section: Surface Coatingsupporting

confidence: 92%

Mechanisms of Genotoxicity of Particles and Fibers

Schins

2002

Inhalation Toxicology

226

108

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With regard to genotoxicity testing and cancer risk assessment, particles and fibers form a rather specific group among all toxicants. First, the physicochemical behavior of fibrous and nonfibrous particles is usually very different from that of nonparticulate, chemical carcinogens. Reactive oxygen species (ROS) are believed to play a major role in primary genotoxicity of particles, which may derive from their surface properties, the presence of transition metals, intracellular iron mobilization, and lipid peroxidation. Other aspects relevant to primary genotoxicity are particle size, shape, crystallinity (e.g., silica), and solubility, and may also include particle uptake, interaction with cell division machinery (e.g., asbestos), and the presence of mutagens carried with the particle (e.g., diesel exhaust particles, DEP). Excessive and persistent formation of ROS from inflammatory cells is considered as the hallmark of the secondary genotoxicity of nonfibrous and fibrous particles. Since lung inflammation is known to occur and persist only at sufficient particle dose, this secondary pathway is considered to contain a threshold (Greim et al., 2001). Identification of (mechanisms of) particle genotoxicity has been/can be achieved via (1) acellular assays, (2) in vitro tests, (3) in vivo studies, usually in mice or rats, and finally (4) biomarker studies in humans with (occupational) exposure. The significance of acellular assays and biomarker studies for risk assessment is limited, but has provided some mechanistic insights (e.g., in oxidant generating properties of quartz and asbestos) and may also contribute to hazard identification. In vitro studies have lead to identification of primary genotoxic properties of particles, whereas recent in vivo studies provide further support for the correlation between particle-induced lung inflammation and secondary genotoxicity. Proper risk assessment of particles necessitates identification of the relative impact of primary versus secondary genotoxicity in realistic exposure conditions. However, since it is impossible to discern between primary and secondary genotoxicity with current in vivo tests, concomitant in vitro assays are required to determine primary genotoxicity. In vivo tests should ideally be designed using different doses to allow dose-effect analysis for both inflammation and genotoxicity.

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Section: Surface Coatingsupporting

confidence: 92%

Mechanisms of Genotoxicity of Particles and Fibers

Schins

2002

Inhalation Toxicology

226

108

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“…After respiration in the lung, many of the C 60 particles become coated by lung surfactant, such as dipalmitoylphosphatidylcholine (DPPC), before being taken up by macrophage cells. Although this surfactant aids dispersion of the C 60 prior to uptake, it signiWcantly alters ingestion and degradation by the cell [25], thus exposing the surface of the C 60 agglomerates. We used THF as a solvent to disperse the C 60 prior to dilution in cell culture medium.…”

Section: Discussionmentioning

confidence: 99%

Uptake of C60 by human monocyte macrophages, its localization and implications for toxicity: Studied by high resolution electron microscopy and electron tomography

et al. 2006

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“…Research with DPPC as the protective component indicates that the protection lasts for only 3 days in vitro because the particle coating is destroyed by enzymatic digestion (either by phospolipase A 2 activity or by AM lysosomal enzymes) [31][32][33]. One problem with surfactant overproduction is that sustained and uncontrolled over a period of time, it can become a pathological feature of silica exposure.…”

Section: Modification Of Silica Toxicity By Lung Surfactantmentioning

confidence: 99%

Silica binding and toxicity in alveolar macrophages

Hamilton

Thakur

Holian

2008

Free Radical Biology and Medicine

332

242

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Inhalation of the crystalline form of silica is associated with a variety of pathologies from acute lung inflammation to silicosis, in addition to autoimmune disorders and cancer. Basic science researchers looking at the mechanisms involved with the earliest initiators of disease are focused on how the alveolar macrophage (AM) interacts with the inhaled silica particle and the consequences of silicainduced toxicity on the cellular level. Based on experimental results, several rationales have been developed on exactly how crystalline silica particles are toxic to the macrophage cell that is functionally responsible for clearance of the foreign particle. For example, silica is capable of producing reactive oxygen species (ROS) either directly (on the particle surface) or indirectly (produced by the cell as a response to silica) triggering cell-signaling pathways initiating cytokine release and apoptosis. With murine macrophages, reactive nitrogen species (RNS) are produced in the initial respiratory burst in addition to ROS. An alternative explanation for silica toxicity includes lysosomal permeability, where silica disrupts the normal internalization process leading to cytokine release and cell death. Still other research has focused on the cell surface receptors (collectively known as scavenger receptors) involved in silica binding and internalization. The silica-induced cytokine release and apoptosis is described as the function of receptor-mediated signaling rather than free radical damage. Current research ideas on silica toxicity and binding in the alveolar macrophage are reviewed and discussed.

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Phospholipid surfactant adsorption by respirable quartz and in vitro expression of cytotoxicity and DNA damage

Cited by 24 publications

References 9 publications

Mechanisms of Genotoxicity of Particles and Fibers

Mechanisms of Genotoxicity of Particles and Fibers

Uptake of C60 by human monocyte macrophages, its localization and implications for toxicity: Studied by high resolution electron microscopy and electron tomography

Silica binding and toxicity in alveolar macrophages

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