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Cytotoxic and inflammatory potential of size-fractionated particulate matter collected repeatedly within a small urban area.
Part Fibre Toxicol. 2015 Jul 16; 12:24.PF

Abstract

BACKGROUND

Exposure to coarse, fine, and ultrafine particles is associated with adverse population health impacts. We investigated whether size-fractionated particles collected repeatedly in the vicinity of industrial (steel mills and associated coking operations, wastewater treatment), high traffic, and residential areas display systematic differences in biological potency.

METHODS

Particulate matter (PM<0.1, PM0.1-0.5, PM0.5-2.5, PM2.5-10, PM>10) samples collected at sites within Windsor, Ontario, were screened for biological potency in human A549 lung epithelial and murine J774A.1 macrophage-like cells using cytotoxicity bioassays (cellular ATP, resazurin reduction, lactate dehydrogenase (LDH) release), cytokine production, and transcript profiles. Potency was determined from the slope of each dose-effect relationship.

RESULTS

Cytotoxic potency varied across size fractions and within a fraction across sites and sampling periods, suggesting that particle composition, in addition to size and mass, affected particle toxicity. While ATP and LDH profiles showed some similarity, resazurin reduction (a measure of metabolic activity) exhibited a unique pattern of response, indicating that the cytotoxicity assays were sensitive to distinct particle characteristics. Chemical speciation varied in relation to prevailing winds, consistent with enrichment of source emissions (e.g. higher metal and polycyclic aromatic hydrocarbon content downwind of the industrial site). Notwithstanding this variability, site-dependent differences in particle toxicity were evident, including greater potency of coarse fractions at the industrial site and of ultrafine particles at the traffic site (Site × Size interactions, p < 0.05). Regression of potency against particle constituents revealed correlations between resazurin reduction, induction of metal-responsive genes, and metal content, which were particularly strong for the coarse fraction, and between cytokine release and endotoxin, suggesting that these factors were important drivers of biological effects that explain, at least in part, the contrasting potencies of particles compared on an equivalent mass basis.

CONCLUSIONS

The data show that 1) particle potency and composition can exhibit significant temporal variation in relation to source contributions; 2) sources may differentially impact the potency of specific size fractions; and 3) particle constituents, notably metals and endotoxin, may elicit distinct biological responses. Together, the data are consistent with the notion that sources and composition, in addition to size and mass concentration, are relevant to particle toxicity.

Authors+Show Affiliations

Inhalation Toxicology Laboratory, Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, 0802B Tunney's Pasture, Ottawa, ON, K1A 0K9, Canada. errol.thomson@hc-sc.gc.ca.Inhalation Toxicology Laboratory, Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, 0802B Tunney's Pasture, Ottawa, ON, K1A 0K9, Canada. dalibor.breznan@hc-sc.gc.ca.Inhalation Toxicology Laboratory, Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, 0802B Tunney's Pasture, Ottawa, ON, K1A 0K9, Canada. subramanian.karthikeyan@hc-sc.gc.ca.Inhalation Toxicology Laboratory, Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, 0802B Tunney's Pasture, Ottawa, ON, K1A 0K9, Canada. christine.mackinnon-roy@cihr-irsc.gc.ca.Analysis and Air Quality Section, Air Quality Research Division, Atmospheric Science and Technology Directorate, Environment Canada, Ottawa, ON, K1A 0H3, Canada. jean-pierre.charland@ec.gc.ca.Analysis and Air Quality Section, Air Quality Research Division, Atmospheric Science and Technology Directorate, Environment Canada, Ottawa, ON, K1A 0H3, Canada. ewa.dabek@ec.gc.ca.Analysis and Air Quality Section, Air Quality Research Division, Atmospheric Science and Technology Directorate, Environment Canada, Ottawa, ON, K1A 0H3, Canada. valbona.celo@ec.gc.ca.Mechanistic Studies Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, K1A 0K9, Canada. premkumari.kumarathasan@hc-sc.gc.ca.Air Quality Processes Research Section, Air Quality Research Division, Atmospheric Science and Technology Directorate, Environment Canada, Toronto, ON, M3H 5T4, Canada. jeff.brook@ec.gc.ca.Inhalation Toxicology Laboratory, Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, 0802B Tunney's Pasture, Ottawa, ON, K1A 0K9, Canada. renaud.vincent@hc-sc.gc.ca.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26178321

Citation

Thomson, Errol M., et al. "Cytotoxic and Inflammatory Potential of Size-fractionated Particulate Matter Collected Repeatedly Within a Small Urban Area." Particle and Fibre Toxicology, vol. 12, 2015, p. 24.
Thomson EM, Breznan D, Karthikeyan S, et al. Cytotoxic and inflammatory potential of size-fractionated particulate matter collected repeatedly within a small urban area. Part Fibre Toxicol. 2015;12:24.
Thomson, E. M., Breznan, D., Karthikeyan, S., MacKinnon-Roy, C., Charland, J. P., Dabek-Zlotorzynska, E., Celo, V., Kumarathasan, P., Brook, J. R., & Vincent, R. (2015). Cytotoxic and inflammatory potential of size-fractionated particulate matter collected repeatedly within a small urban area. Particle and Fibre Toxicology, 12, 24. https://doi.org/10.1186/s12989-015-0099-z
Thomson EM, et al. Cytotoxic and Inflammatory Potential of Size-fractionated Particulate Matter Collected Repeatedly Within a Small Urban Area. Part Fibre Toxicol. 2015 Jul 16;12:24. PubMed PMID: 26178321.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytotoxic and inflammatory potential of size-fractionated particulate matter collected repeatedly within a small urban area. AU - Thomson,Errol M, AU - Breznan,Dalibor, AU - Karthikeyan,Subramanian, AU - MacKinnon-Roy,Christine, AU - Charland,Jean-Pierre, AU - Dabek-Zlotorzynska,Ewa, AU - Celo,Valbona, AU - Kumarathasan,Prem, AU - Brook,Jeffrey R, AU - Vincent,Renaud, Y1 - 2015/07/16/ PY - 2015/03/17/received PY - 2015/07/02/accepted PY - 2015/7/17/entrez PY - 2015/7/17/pubmed PY - 2016/4/2/medline SP - 24 EP - 24 JF - Particle and fibre toxicology JO - Part Fibre Toxicol VL - 12 N2 - BACKGROUND: Exposure to coarse, fine, and ultrafine particles is associated with adverse population health impacts. We investigated whether size-fractionated particles collected repeatedly in the vicinity of industrial (steel mills and associated coking operations, wastewater treatment), high traffic, and residential areas display systematic differences in biological potency. METHODS: Particulate matter (PM<0.1, PM0.1-0.5, PM0.5-2.5, PM2.5-10, PM>10) samples collected at sites within Windsor, Ontario, were screened for biological potency in human A549 lung epithelial and murine J774A.1 macrophage-like cells using cytotoxicity bioassays (cellular ATP, resazurin reduction, lactate dehydrogenase (LDH) release), cytokine production, and transcript profiles. Potency was determined from the slope of each dose-effect relationship. RESULTS: Cytotoxic potency varied across size fractions and within a fraction across sites and sampling periods, suggesting that particle composition, in addition to size and mass, affected particle toxicity. While ATP and LDH profiles showed some similarity, resazurin reduction (a measure of metabolic activity) exhibited a unique pattern of response, indicating that the cytotoxicity assays were sensitive to distinct particle characteristics. Chemical speciation varied in relation to prevailing winds, consistent with enrichment of source emissions (e.g. higher metal and polycyclic aromatic hydrocarbon content downwind of the industrial site). Notwithstanding this variability, site-dependent differences in particle toxicity were evident, including greater potency of coarse fractions at the industrial site and of ultrafine particles at the traffic site (Site × Size interactions, p < 0.05). Regression of potency against particle constituents revealed correlations between resazurin reduction, induction of metal-responsive genes, and metal content, which were particularly strong for the coarse fraction, and between cytokine release and endotoxin, suggesting that these factors were important drivers of biological effects that explain, at least in part, the contrasting potencies of particles compared on an equivalent mass basis. CONCLUSIONS: The data show that 1) particle potency and composition can exhibit significant temporal variation in relation to source contributions; 2) sources may differentially impact the potency of specific size fractions; and 3) particle constituents, notably metals and endotoxin, may elicit distinct biological responses. Together, the data are consistent with the notion that sources and composition, in addition to size and mass concentration, are relevant to particle toxicity. SN - 1743-8977 UR - https://www.unboundmedicine.com/medline/citation/26178321/Cytotoxic_and_inflammatory_potential_of_size_fractionated_particulate_matter_collected_repeatedly_within_a_small_urban_area_ L2 - https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-015-0099-z DB - PRIME DP - Unbound Medicine ER -