Revisiting the paradigm of silica pathogenicity with synthetic quartz crystals: the role of crystallinity and surface disorder.
Exposure to some - but not all - quartz particles is associated to silicosis, lung cancer and autoimmune diseases. What imparts pathogenicity to any single quartz source is however still unclear. Crystallinity and various surface features are implied in toxicity. Quartz dusts used so far in particle toxicology have been obtained by grinding rocks containing natural quartz, a process which affects crystallinity and yields dusts with variable surface states. To clarify the role of crystallinity in quartz pathogenicity we have grown intact quartz crystals in respirable size.



Quartz crystals were grown and compared with a fractured specimen obtained by grinding the largest synthetic crystals and a mineral quartz (positive control). The key physico-chemical features relevant to particle toxicity - particle size distribution, micromorphology, crystallinity, surface charge, cell-free oxidative potential - were evaluated. Membranolysis was assessed on biological and artificial membranes. Endpoints of cellular stress were evaluated on RAW 264.7 murine macrophages by High Content Analysis after ascertaining cellular uptake by bio-TEM imaging of quartz-exposed cells.



Quartz crystals were grown in the submicron (n-Qz-syn) or micron (μ-Qz-syn) range by modulating the synthetic procedure. Independently from size as-grown quartz crystals with regular intact faces did not elicit cellular toxicity and lysosomal stress on RAW 264.7 macrophages, and were non-membranolytic on liposome and red blood cells. When fractured, synthetic quartz (μ-Qz-syn-f) attained particle morphology and size close to the mineral quartz dust (Qz-f, positive control) and similarly induced cellular toxicity and membranolysis. Fracturing imparted a higher heterogeneity of silanol acidic sites and radical species at the quartz surface.



Our data support the hypothesis that the biological activity of quartz dust is not due to crystallinity but to crystal fragmentation, when conchoidal fractures are formed. Besides radical generation, fracturing upsets the expected long-range order of non-radical surface moieties - silanols, silanolates, siloxanes - which disrupt membranes and induce cellular toxicity, both outcomes associated to the inflammatory response to quartz.
Department of Chemistry, University of Torino, Via P. Giuria 7, Turin, 10125, Italy. francesco.turci@unito.it.|"G. Scansetti" Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates, University of Torino, Via P. Giuria 7, Turin, 10125, Italy. francesco.turci@unito.it.
Francesco
F
Turci
Department of Chemistry, University of Torino, Via P. Giuria 7, Turin, 10125, Italy.|"G. Scansetti" Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates, University of Torino, Via P. Giuria 7, Turin, 10125, Italy.
Cristina
C
Pavan
Department of Chemistry, University of Torino, Via P. Giuria 7, Turin, 10125, Italy.|"G. Scansetti" Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates, University of Torino, Via P. Giuria 7, Turin, 10125, Italy.
Riccardo
R
Leinardi
Department of Chemistry, University of Torino, Via P. Giuria 7, Turin, 10125, Italy.|"G. Scansetti" Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates, University of Torino, Via P. Giuria 7, Turin, 10125, Italy.
Maura
M
Tomatis
"G. Scansetti" Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates, University of Torino, Via P. Giuria 7, Turin, 10125, Italy.|Department of Earth Sciences, University of Torino, Via V. Caluso 35, Turin, 10125, Italy.
Linda
L
Pastero
Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Dublin, Belfield, Ireland.
David
D
Garry
Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Dublin, Belfield, Ireland.
Sergio
S
Anguissola
Louvain centre for Toxicology and Applied Pharmacology (LTAP), Université catholique de Louvain, Avenue E. Mounier 52 - bte B1.52.12, Brussels, 1200, Belgium.
Dominique
D
Lison
Department of Chemistry, University of Torino, Via P. Giuria 7, Turin, 10125, Italy.|"G. Scansetti" Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates, University of Torino, Via P. Giuria 7, Turin, 10125, Italy.
Bice
B
Fubini
D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D003460:Crystallization; D004391:Dust; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D051379:Mice; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D010316:Particle Size; D055585:Physical Phenomena; D011791:Quartz / Q000737:chemistry / Q000633:toxicity*; D000067996:RAW 264.7 Cells; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*; D013499:Surface Properties; D018675:Toxicity Tests
D000393:Air Pollutants; D015415:Biomarkers; D004391:Dust; D011791:Quartz; D012822:Silicon Dioxide
Conchoidal fracture; Crystallinity; Membranolysis; Quartz; Radicals; Silanols; Silica; Surface charge; Toxicity