Genotoxicity of diesel-exhaust particles dispersed in simulated pulmonary surfactant

Keane, Michael; Xing, Shuguang; Harrison, Joel C.; Ong, T.; Wallace, W.E.

doi:10.1016/0165-1218(91)90031-g

Cited by 35 publications

(6 citation statements)

References 9 publications

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“…Consistent with this is the evidence presented here and by Singh et al (2004) for greater amounts of PAH-type mutagenicity and PAHs in the A-DEPs compared with SRM 2975. There is ample evidence that the genotoxic activity associated with the EOM of DEPs inhaled into the lung may be bioavailable by virtue of the solubilization and dispersion properties of pulmonary surfactant components (Belisario et al 1984;Keane et al 1991;King et al 1981).…”

Section: Discussionmentioning

confidence: 99%

Bioassay-directed fractionation and salmonella mutagenicity of automobile and forklift diesel exhaust particles.

DeMarini

Brooks

Warren

et al. 2004

Environ Health Perspect

118

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Many pulmonary toxicity studies of diesel exhaust particles (DEPs) have used an automobile-generated sample (A-DEPs) whose mutagenicity has not been reported. In contrast, many mutagenicity studies of DEPs have used a forklift-generated sample (SRM 2975) that has been evaluated in only a few pulmonary toxicity studies. Therefore, we evaluated the mutagenicity of both DEPs in Salmonella coupled to a bioassay-directed fractionation. The percentage of extractable organic material (EOM) was 26.3% for A-DEPs and 2% for SRM 2975. Most of the A-EOM (~55%) eluted in the hexane fraction, reflecting the presence of alkanes and alkenes, typical of uncombusted fuel. In contrast, most of the SRM 2975 EOM (~58%) eluted in the polar methanol fraction, indicative of oxygenated and/or nitrated organics derived from combustion. Most of the direct-acting, base-substitution activity of the A-EOM eluted in the hexane/dichloromethane (DCM) fraction, but this activity eluted in the polar methanol fraction for the SRM 2975 EOM. The direct-acting frameshift mutagenicity eluted across fractions of A-EOM, whereas > 80% eluted only in the DCM fraction of SRM 2975 EOM. The A-DEPs were more mutagenic than SRM 2975 per mass of particle, having 227 times more polycyclic aromatic hydrocarbon-type and 8-45 more nitroarene-type mutagenic activity. These differences were associated with the different conditions under which the two DEP samples were generated and collected. A comprehensive understanding of the mechanisms responsible for the health effects of DEPs requires the evaluation of DEP standards for a variety of end points, and our results highlight the need for multidisciplinary studies on a variety of representative samples of DEPs.

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Section: Discussionmentioning

confidence: 99%

Bioassay-directed fractionation and salmonella mutagenicity of automobile and forklift diesel exhaust particles.

DeMarini

Brooks

Warren

et al. 2004

Environ Health Perspect

118

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“…Earlier, the same research group investigated the role of surfactant in the genotoxicity of DEP using the Salmonella mutagenicity test and the sister chromatid exchange (SCE) assay in V79 cells (Keane et al, 1991). In both assays, DEP dispersed in aqueous suspension containing DDPC or dichloromethane extracts of DEP were found to have similar genotoxicity.…”

Section: Surface Coatingmentioning

confidence: 97%

Mechanisms of Genotoxicity of Particles and Fibers

Schins

2002

Inhalation Toxicology

228

108

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With regard to genotoxicity testing and cancer risk assessment, particles and fibers form a rather specific group among all toxicants. First, the physicochemical behavior of fibrous and nonfibrous particles is usually very different from that of nonparticulate, chemical carcinogens. Reactive oxygen species (ROS) are believed to play a major role in primary genotoxicity of particles, which may derive from their surface properties, the presence of transition metals, intracellular iron mobilization, and lipid peroxidation. Other aspects relevant to primary genotoxicity are particle size, shape, crystallinity (e.g., silica), and solubility, and may also include particle uptake, interaction with cell division machinery (e.g., asbestos), and the presence of mutagens carried with the particle (e.g., diesel exhaust particles, DEP). Excessive and persistent formation of ROS from inflammatory cells is considered as the hallmark of the secondary genotoxicity of nonfibrous and fibrous particles. Since lung inflammation is known to occur and persist only at sufficient particle dose, this secondary pathway is considered to contain a threshold (Greim et al., 2001). Identification of (mechanisms of) particle genotoxicity has been/can be achieved via (1) acellular assays, (2) in vitro tests, (3) in vivo studies, usually in mice or rats, and finally (4) biomarker studies in humans with (occupational) exposure. The significance of acellular assays and biomarker studies for risk assessment is limited, but has provided some mechanistic insights (e.g., in oxidant generating properties of quartz and asbestos) and may also contribute to hazard identification. In vitro studies have lead to identification of primary genotoxic properties of particles, whereas recent in vivo studies provide further support for the correlation between particle-induced lung inflammation and secondary genotoxicity. Proper risk assessment of particles necessitates identification of the relative impact of primary versus secondary genotoxicity in realistic exposure conditions. However, since it is impossible to discern between primary and secondary genotoxicity with current in vivo tests, concomitant in vitro assays are required to determine primary genotoxicity. In vivo tests should ideally be designed using different doses to allow dose-effect analysis for both inflammation and genotoxicity.

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“…This could lead to conditioning of particle surfaces which may affect their expression of cytotoxicity or genotoxicity [Wallace et al, 2006]. This was seen for diesel exhaust particles (DEP) and also silica particles conditioned by DPPC [Keane et al, 1991;Murray et al, 2005;Wallace et al, 2006]. A recent study by Foucaud et al (2007) demonstrated that the oxidative potential of Printex 90 carbon black nanoparticles can be modified by dispersion in medium containing DPPC and BSA.…”

Section: Dispersion Of Hipco Swcnt and Asbestos Fibresmentioning

confidence: 99%

SWCNT suppress inflammatory mediator responses in human lung epithelium in vitro

Herzog¹,

Byrne²,

Casey³

et al. 2009

Toxicology and Applied Pharmacology

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Genotoxicity of diesel-exhaust particles dispersed in simulated pulmonary surfactant

Cited by 35 publications

References 9 publications

Bioassay-directed fractionation and salmonella mutagenicity of automobile and forklift diesel exhaust particles.

Bioassay-directed fractionation and salmonella mutagenicity of automobile and forklift diesel exhaust particles.

Mechanisms of Genotoxicity of Particles and Fibers

SWCNT suppress inflammatory mediator responses in human lung epithelium in vitro

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