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Comparative cytotoxicity of respirable surface-treated/untreated calcium carbonate rock dust particles in vitro.

ABSTRACT: Calcium carbonate rock dust (RD) is used in mining to reduce the explosivity of aerosolized coal. During the dusting procedures, potential for human exposure occurs, raising health concerns. To improve RD aerosolization, several types of anti-caking surface treatments exist. The aim of the study was to evaluate cytotoxicity of four respirable RD samples: untreated/treated limestone (UL/TL), untreated/treated marble (UM/TM), and crystalline silica (SiO2) as a positive control in A549 and THP-1 transformed human cell lines. Respirable fractions were generated and collected using FSP10 high flow-rate cyclone samplers. THP-1 cells were differentiated with phorbol-12-myristate-13-acetate (20?ng/ml, 48?h). Cells were exposed to seven different concentrations of RD and SiO2 (0-0.2?mg/ml). RD caused a slight decrease in viability at 24 or 72?h post-exposure and were able to induce inflammatory cytokine production in A549 cells, however, with considerably less potency than SiO2. In THP-1 cells at 24?h, there was significant dose-dependent lactate dehydrogenase, inflammatory cytokine and chemokine release. Caspase-1 activity was increased in SiO2- and, on a lesser scale, in TM- exposed cells. To test if the increased toxicity of TM was uptake-related, THP-1 cells were pretreated with Cytochalasin D (CytD) or Bafilomycin A (BafA), followed by exposure to RD or SiO2 for 6?h. CytD blocked the uptake and significantly decreased cytotoxicity of all particles, while BafA prevented caspase-1 activation but not cytotoxic effects of TM. Only TM was able to induce an inflammatory response in THP-1 cells, however it was much less pronounced compared to silica.

SUBMITTER: Khaliullin TO

PROVIDER: S-EPMC6438615 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Comparative cytotoxicity of respirable surface-treated/untreated calcium carbonate rock dust particles in vitro.

Khaliullin Timur O TO Kisin Elena R ER Yanamala Naveena N Guppi Supraja S Harper Martin M Lee Taekhee T Shvedova Anna A AA

Toxicology and applied pharmacology 20181025

Calcium carbonate rock dust (RD) is used in mining to reduce the explosivity of aerosolized coal. During the dusting procedures, potential for human exposure occurs, raising health concerns. To improve RD aerosolization, several types of anti-caking surface treatments exist. The aim of the study was to evaluate cytotoxicity of four respirable RD samples: untreated/treated limestone (UL/TL), untreated/treated marble (UM/TM), and crystalline silica (SiO<sub>2</sub>) as a positive control in A549 a ...[more]

PMID: 30393145

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Project description:BackgroundRespirable stone- and mineral particles may be a major constituent in occupational and ambient air pollution and represent a possible health hazard. However, with exception of quartz and asbestos, little is known about the toxic properties of mineral particles. In the present study, the pro-inflammatory and cytotoxic responses to six stone particle samples of different composition and with diameter below 10 μm were assessed in human bronchial epithelial cells (HBEC3-KT), THP-1 macrophages and a HBEC3-KT/THP-1 co-culture. Moreover, particle-induced lysis of human erythrocytes was assessed to determine the ability of the particles to lyse biological membranes. Finally, the role of the NLRP3 inflammasome was assessed using a NLRP3-specific inhibitor and detection of ASC oligomers and cleaved caspase-1 and IL-1β. A reference sample of pure α-quartz was included for comparison.ResultsSeveral stone particle samples induced a concentration-dependent increase in cytotoxicity and secretion of the pro-inflammatory cytokines CXCL8, IL-1α, IL-1β and TNFα. In HBEC3-KT, quartzite and anorthosite were the most cytotoxic stone particle samples and induced the highest levels of cytokines. Quartzite and anorthosite were also the most cytotoxic samples in THP-1 macrophages, while anorthosite and hornfels induced the highest cytokine responses. In comparison, few significant differences between particle samples were detected in the co-culture. Adjusting responses for differences in surface area concentrations did not fully account for the differences between particle samples. Moreover, the stone particles had low hemolytic potential, indicating that the effects were not driven by membrane lysis. Pre-incubation with a NLRP3-specific inhibitor reduced stone particle-induced cytokine responses in THP-1 macrophages, but not in HBEC3-KT cells, suggesting that the effects are mediated through different mechanisms in epithelial cells and macrophages. Particle exposure also induced an increase in ASC oligomers and cleaved caspase-1 and IL-1β in THP-1 macrophages, confirming the involvement of the NLRP3 inflammasome.ConclusionsThe present study indicates that stone particles induce cytotoxicity and pro-inflammatory responses in human bronchial epithelial cells and macrophages, acting through NLRP3-independent and -dependent mechanisms, respectively. Moreover, some particle samples induced cytotoxicity and cytokine release to a similar or greater extent than α-quartz. Thus, these minerals warrant further attention in future research.

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Comparative cytotoxicity of respirable surface-treated/untreated calcium carbonate rock dust particles in vitro.

Publications

Comparative cytotoxicity of respirable surface-treated/untreated calcium carbonate rock dust particles in vitro.

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