Genotoxicity of airborne particulate matter: the role of cell-particle interaction and of substances with adduct-forming and oxidizing capacity.
Exposure to particulate matter (PM) is associated with several health effects including lung cancer. However, the mechanisms of particle-induced carcinogenesis are not fully understood. The main aim of this study was to investigate the genotoxicity of PM in relation to particle-cell interactions and to study the effect of removal of DNA-damaging substances by extraction of PM with different solvents. Genotoxicity was analyzed by means of the comet assay after exposure of cultured human fibroblasts to urban dust particles (SRM 1649). It was found that PM induced DNA damage in a dose-dependent manner and that cells interacting with PM suffered more DNA single-strand breaks relative to other cells. The genotoxicity of PM was significantly reduced after extraction with dichloromethane (DCM), dimethyl sulfoxide (DMSO) and water, but not with acetone and hexane. However, the insoluble particle core still induced DNA single-strand breaks. The extracts were further investigated in cell-free systems. Analysis of aromatic DNA adducts with 32P-HPLC showed that the DMSO and DCM extracts contained most of the DNA-reactive polyaromatic compounds (PACs). Further, the formation of 8-oxo-2'-deoxyguanosine (8-oxodG) upon incubation of the extracts with 2'-deoxyguanosine (dG) showed that the water extract contained most of the oxidizing substances. Thus, the genotoxicity of PM was caused both by adduct-forming PACs and oxidizing substances as well as the insoluble particle-core. This study showed that all these factors together contribute to explaining the mechanisms of PM genotoxicity.
Karlsson
Hanna L
HL
Unit for Analytical Toxicology, Department of Biosciences at Novum, Karolinska Institutet, SE-14157 Huddinge, Stockholm, Sweden.
Nygren
Jonas
J
Möller
Lennart
L
D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D020552:Comet Assay; D018736:DNA Adducts; D004249:DNA Damage; D003849:Deoxyguanosine / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D009152:Mutagenicity Tests; D016877:Oxidants / Q000378:metabolism; D010316:Particle Size; D051381:Rats; D012997:Solvents / Q000737:chemistry
D000393:Air Pollutants; D018736:DNA Adducts; D016877:Oxidants; D012997:Solvents; D007501:Iron; D003849:Deoxyguanosine