DNA binding of polycyclic aromatic hydrocarbons in a human bronchial epithelial cell line treated with diesel and gasoline particulate extracts and benzo[a]pyrene

Abstract

Particulate matter of vehicle exhaust is known to contain carcinogenic compounds such as polycyclic aromatic hydrocarbons (PAH) and is suggested to increase lung cancer risk in humans. This study examines the differences in diesel and gasoline-derived PAH binding to DNA in a human bronchial epithelial cell line (BEAS-2B). Particulate matter (PM) of gasoline exhaust was collected from passenger cars on filters and semi-volatile compounds on polyurethane foam (PUF). The soluble organic fraction (SOF) extracted from the particles was used to expose the cells and to perform PAH analysis. Gasoline extracts, benzo[a]pyrene (B[a]P) and reference materials (SRM 1650 and 1587) were used to study dose-dependent adduct formation in BEAS-2B cells. The levels of DNA adducts were in good accord with the 10 DNA adduct-forming PAH concentrations analyzed in the extracts. Gasoline extracts, SRM 1650, SRM 1587 and B[a]P formed DNA adducts dose-dependently in BEAS-2B cells. The time-dependent DNA adduct formation of 5.0 micro M B[a]P was lower than that of 2.5 micro M B[a]P. The results of this study indicate that reformulated and standard diesel fuels formed about 11- and 31-fold more adducts than gasoline, respectively, when PAH-DNA adduct levels were calculated on an emission basis (adducts/mg PM/km), whereas on a particulate basis (adducts/mg PM) no difference between the diesel and gasoline extracts was observed. We conclude that the genotoxicity of diesel fuel is based on higher particulate emission rates compared to gasoline emission and although the concentration of PAH compounds was higher in diesel particulate extracts, DNA binding by the gasoline particulate-bound PAH compounds was more pronounced than that by the diesel particulate-bound PAH compounds.

Aero-dispersed mutagenicity attributed to particulate and semi volatile phase in an urban environment

“…In particular, PM1 was responsible for approximately 80% of the observed effects at various 239 sampling localities (Novak et al, 2014), and the fine particles generally showed higher mutagenicity 240 (Claxton et al, 2004;Claxton and Woodall, 2007b;Lemos et al, 2012). The gas phase mutagenicity was very 241 low and often indeterminable, with the exception of particular sampling sites such as industrial sites (Du 242 Four et al, 2005) and exhaust emissions from gasoline-and diesel-powered passengers cars (Pohjola et al, 2003a;Pohjola et al, 2003b). The contribution of the gas phase with respect to the particulate phase seems 244 to be higher during summer and related to the major PAHs content (Du Four et al, 2004;Kennedy et al, 245 2010).…”

Mechanistic Studies of the Bypass of a Bulky Single-base Lesion Catalyzed by a Y-family DNA Polymerase

“…1-NP, one of the most abundant polycyclic aromatic hydrocarbons, is a product of incomplete diesel and gasoline combustion (1,29,30). There are two known pathways by which 1-NP is metabolized: nitro reduction (Scheme 1) and C-hydroxylation.…”

Use of a fluorescent phosphoprotein dye to characterize oxidative stress-induced signaling pathway components in macrophage and epithelial cultures exposed to diesel exhaust particle chemicals

“…This is in keeping with the ability of the quinones to participate in redox cycling reactions after cellular uptake, while PAHs need to be enzymatically converted to oxy-derivatives before being rendered functionally active [32,33]. Previously published studies demonstrating that environmental polycyclic aromatic hydrocarbons, including DEP extracts, are capable of inducing cytochrome P450 1A1 and 1B1 expression in human macrophages and bronchial epithelial cells supports this notion [1,34,35]. While evidence has been provided that this is also true in BEAS-2B cells, the same needs to be demonstrated for RAW 264.7 cells.…”