Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden. Electronic address: .
Toxicology and Applied Pharmacology (Impact Factor: 3.71). 12/2012; 266(3). DOI: 10.1016/j.taap.2012.11.026
Source: PubMed


Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNA damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower concentrations of air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al. 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs.

1 Follower
20 Reads
  • Source
    • "Our study, together with data from studies on PAH mixtures described in Jarvis et al. (2013), shows that it is important to achieve a better understanding of the mechanistic interactions of genotoxic mixtures in the future. Apart from the experimental findings in our study and those described in Jarvis et al. (2013), evaluation of genotoxic response to mixture of pesticides in the field has furthermore been conducted with the comet assay. Remor et al. (2009) found significant genotoxic effects in peripheral blood leukocytes from workers exposed to a mixture of genotoxic pesticides, illustrating that mixture genotoxicity is relevant at realistic exposure concentrations, and not only in regard to the high exposure concentrations used in our rapid in vitro study. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Assessment of genotoxic properties of chemicals is mainly conducted only for single chemicals, without taking mixture genotoxic effects into consideration. The current study assessed mixture effects of the three known genotoxic chemicals, 2,4-dichlorophenoxyacetic acid (2,4-D), acrylamide (AA), and maleic hydrazide (MH), in an experiment with a fixed ratio design setup. The genotoxic effects were assessed with the single-cell gel electrophoresis assay (comet assay) for both single chemicals and the ternary mixture. The concentration ranges used were 0-1.4, 0-20, and 0-37.7 mM for 2,4-D, AA, and MH, respectively. Mixture toxicity was tested with a fixed ratio design at a 10:23:77% ratio for 2.4-D:AA:MH. Results indicated that the three chemicals yielded a synergistic mixture effect. It is not clear which mechanisms are responsible for this interaction. A few possible interactions are discussed, but further investigations including in vivo studies are needed to clarify how important these more-than-additive effects are for risk assessment.
    Journal of Toxicology and Environmental Health Part A 03/2015; 78(6):369-80. DOI:10.1080/15287394.2014.983626 · 2.35 Impact Factor
  • Source
    • "They have drawn considerable attention by a number of international environmental protection agencies and scientific communities because of their adverse effects on human health and environment [1] [2] [3]. PAHs find their way into human organs through breathing, diet and skin exposure, and can cause lung cancer, upper digestive tract cancer, skin cancer, arteriosclerosis, etc. [4] [5]. Hence, the United States Environmental Protection Agency (US EPA) has listed 16 PAHs as priority control organic pollutants. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The highlight of this work is that solid-phase microextraction (SPME) coupled with gas chromatography/mass spectrometry (GC/MS) was firstly introduced to the determination of the polycyclic aromatic hydrocarbons (PAHs) in leather products. In this work, a home-made poly(dimethylsiloxane) (PDMS) fiber was employed as the extraction phase to extract 9 sample PAHs in leather products by headspace SPME. Method development including the optimization of extraction, desorption process, and salt addition was done. The analytical figures of merit showed that the sampling linear ranges of the proposed method were 0.1–20 μg/L, and the detection limits of 9 PAHs were lower than 0.05 μg/L except chrysene with 0.12 μg/L. The developed method presented a simple, rapid, sensitive, and inexpensive method to detect PAHs in leather and was successfully applied to the detection of PAHs in three kinds of leather products. The spiked recoveries for 9 PAHs ranging from 81.7% to 124.9% also demonstrated the accuracy of the proposed method.
    Microchemical Journal 01/2014; 112:159–163. DOI:10.1016/j.microc.2013.10.010 · 2.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In order to investigate the genotoxicity of the micron LiFePO4 rice granule, an electrochemical biosensor based on determination of guanine (G) oxidative damage induced by the LiFePO4/HCl/K2S2O8 system was developed. In the LiFePO4/HCl/K2S2O8 system, the reaction of the micron LiFePO4 rice granule with HCl produced Fe2+, and the produced Fe2+ would further react with S2O82-, generating sulfate radical (SO4 center dot-) which could severely damage the guanine bases that was immobilized on a glassy carbon electrode (GCE) surface by electro-deposition. The square wave voltammetry (SWV) signal change of the guanine bases was used to monitor the guanine damage. The present work provided a simple electrochemical approach for screening the potential genotoxicity of particulate matters and chemicals in vitro, and it also had potential application in investigating some chemicals anti-oxidation property.
    Sensors and Actuators B Chemical 03/2014; 192:234–238. DOI:10.1016/j.snb.2013.10.105 · 4.10 Impact Factor
Show more