Comparison of mutagenicity and calf thymus DNA adducts formed by the particulate and semivolatile fractions of vehicle exhausts

Abstract

In this study we compared the ability of extractable organic material from particulate and semivolatile fractions of gasoline emission to induce mutations in bacteria and form adducts with calf thymus (CT) DNA with corresponding data obtained from diesel exhaust. Exhaust particles from gasoline-powered passenger cars were collected on filters and semivolatile compounds were collected on polyurethane foam (PUF). The mutagenicity of the soluble organic fraction (SOF) was determined in Salmonella typhimurium strain TA98 and the DNA binding of aromatic compounds in the extracts was assessed by in vitro incubations with CT DNA and rat liver S9 (oxidative activation) or xanthine oxidase (reductive activation) followed by butanol-enhanced (32)P-postlabeling analysis. Semivolatile fractions of gasoline emission collected on PUF formed more CT DNA adducts than filter extracts under all reaction conditions, but showed a lower mutagenic potential than the corresponding particulate samples. This suggests that the capacity of PUF to collect exhaust particle-derived compounds and/or the efficiency of xanthine oxidase and enzymes in the rat liver S9 to activate these compounds to DNA binding metabolites was higher than expected. Gasoline extracts, benzo[a]pyrene and diesel particulate matter (SRM 1650) formed more S9-mediated DNA adducts as their dose increased, although a linear dose-response was not observed for the gasoline exhausts. Lower concentrations of gasoline and diesel extracts bound to DNA with greater efficiency than did 8-fold higher doses, suggesting complex interactions and/or an inhibition of S9 enzyme activities by the high doses. Diesel extracts formed higher levels of adducts than gasoline extracts, especially with the reductive activation system, suggesting that diesel extracts contain high levels of nitro-polycyclic aromatic hydrocarbons (nitro-PAHs). The higher direct-acting Salmonella mutagenicity in diesel extracts in comparison with gasoline extracts is consistent with diesel extracts containing higher concentrations of nitro-PAHs. The results of this study indicate that diesel extracts are more mutagenic and form more DNA adducts than gasoline extracts and that the effects of extract dose on DNA adduct formation are complex.

Mutagenicity of diesel exhaust particles mediated by cell–particle interaction in mammalian cells

“…Most Ames tests have demonstrated that DEPs and their extracts are mutagenic and closely related to the generation of reactive oxygen species (Pohjola et al, 2003;Tsurudome et al, 1999;DeMarini et al, 2004). However, there is less direct evidence to demonstrate the mutagenicity of DEPs in mammalian cells.…”

“…Genotoxicity is thought to be crucial for the development of malignancy. Numerous in vivo and in vitro studies have suggested that size distribution, surface properties, and adsorbed chemicals are important criteria for the genotoxicity of DEPs (Stoeger et al, 2006;Pohjola et al, 2003). It has been reported that DEP exposure causes DNA and chromosomal damages including bulky DNA adducts, oxidized bases, deletions, and chromosomal aberrations, which may lead to a broad spectrum of mutation (DeMarini et al, 2004;Tsurudome et al, 1999;Muller et al, 2004).…”

Activated Toxicity of Diesel Particulate Extract by Ultraviolet A Radiation in Mammalian Cells: Role of Singlet Oxygen

“…Most Ames tests have demonstrated that DEPs and DPEs are mutagenic and are closely related to the generation of ROS (DeMarini et al 2004; Pohjola et al 2003; Tsurudome et al 1999). At doses greater than 100 μg/mL, Li and colleagues found that the organic extracts of DEPs were able to generate ROS and induce cell death and apoptosis in macrophages (Hiura et al 1999; Li et al 2002).…”

Particulate matter neurotoxicity in culture is size-dependent

“…Numerous animal studies indicate that inhalation of PM results in inflammatory toxicity in the airways and cardiovascular effects (Chen et al 2010; deHaar et al 2006; Maier et al 2008; Oberdorster et al 2000). Although the historical focus of PM toxicity has been on these cardiopulmonary targets, it is now appreciated that inhaled nano-size particulates can quickly exit the lungs and enter the circulation where they distribute (i.e., liver, kidneys, testes, lymph nodes, brain) (Kreyling et al 2004; Oberdorster et al 2002a; Oberdorster et al 2002b) and these organ systems through oxidative stress (Pohjola et al 2003; Samet et al 2004; Schulz 2006). …”