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Cao, X. ; Padoan, S. ; Binder, S. ; Bauer, S. ; Orasche, J. ; Rus, C.M.* ; Mudan, A.* ; Huber, A. ; Kuhn, E. ; Oeder, S. ; Lintelmann, J. ; Adam, T. ; Di Bucchianico, S. ; Zimmermann, R.

A comparative study of persistent DNA oxidation and chromosomal instability induced in vitro by oxidizers and reference airborne particles.

Mutat. Res. - Gen. Tox. Environ. Mutag. 874-875:503446 (2022)
Postprint DOI PMC
Open Access Green
Adverse health effects driven by airborne particulate matter (PM) are mainly associated with reactive oxygen species formation, pro-inflammatory effects, and genome instability. Therefore, a better understanding of the underlying mechanisms is needed to evaluate health risks caused by exposure to PM. The aim of this study was to compare the genotoxic effects of two oxidizing agents (menadione and 3-chloro-1,2-propanediol) with three different reference PM (fine dust ERM-CZ100, urban dust SRM1649, and diesel PM SRM2975) on monocytic THP-1 and alveolar epithelial A549 cells. We assessed DNA oxidation by measuring the oxidized derivative 8-hydroxy-2'-deoxyguanosine (8-OHdG) following short and long exposure times to evaluate the persistency of oxidative DNA damage. Cytokinesis-block micronucleus cytome assay was performed to assess chromosomal instability, cytostasis, and cytotoxicity. Particles were characterized by inductively coupled plasma mass spectrometry in terms of selected elemental content, the release of ions in cell medium and the cellular uptake of metals. PM deposition and cellular dose were investigated by a spectrophotometric method on adherent A549 cells. The level of lipid peroxidation was evaluated via malondialdehyde concentration measurement. Despite differences in the tested concentrations, deposition efficiency, and lipid peroxidation levels, all reference PM samples caused oxidative DNA damage to a similar extent as the two oxidizers in terms of magnitude but with different oxidative DNA damage persistence. Diesel SRM2975 were more effective in inducing chromosomal instability with respect to fine and urban dust highlighting the role of polycyclic aromatic hydrocarbons derivatives on chromosomal instability. The persistence of 8-OHdG lesions strongly correlated with different types of chromosomal damage and revealed distinguishing sensitivity of cell types as well as specific features of particles versus oxidizing agent effects. In conclusion, this study revealed that an interplay between DNA oxidation persistence and chromosomal damage is driving particulate matter-induced genome instability.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genotoxicity ; Micronuclei ; Oxidative Dna Damage ; Oxidizing Agents ; Reference Particulate Matter
ISSN (print) / ISBN 1383-5718
e-ISSN 1388-2120
Journal Mutation Research / Genetic Toxicology and Environmental Mutagenesis
Quellenangaben Volume: 874-875, Issue: , Pages: , Article Number: 503446 Supplement: ,
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Cooperation Group Comprehensive Molecular Analytics (CMA)
CF Metabolomics & Proteomics (CF-MPC)
Grants Helmholtz Virtual Institute of Complex Molecular Systems in Environmental Health (HICE) via the Helmholtz Association of German Research Centers (HFG)
China Scholarship Council (CSC)