Benzene is a common environmental carcinogen that induces leukemia. Studies suggest that metabolic disorder has a relationship with the toxicity of benzene. Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis. However, the upstream and downstream regulatory mechanisms of PKM2 in benzene-induced hematotoxicity and the therapeutic effects of targeting PKM2 in vivo are unclear. This study aims to provide insights into the new mechanism of benzene-induced hematotoxicity and reveal the therapeutic significance of targeting PKM2. Herein, we demonstrated that PKM2-dependent glycolysis contributes to benzene-induced hematotoxicity by regulating inflammation reaction. Mechanistically, acetylated proteomics revealed that 1,4-benzoquinone (1,4-BQ) induced acetylation of PKM2 at position K66, and this modification contributed to the increase of PKM2 expression and can be inhibited by inhibition of acetyltransferase GCN5. Meanwhile, the elevated PKM2 was shown to prompt the activation of nuclear phosphorylated Stat3 (p-Stat3) and IL17A. Clinically, pharmacological inhibition of PKM2 alleviated the blood toxicity induced by benzene, which was mainly characterized by an increase in routine blood parameters and improvement of hematopoietic imbalance. Besides, elevated PKM2 is a promising biomarker in people occupationally exposed to benzene. Overall, we identified PKM2/p-Stat3/IL-17A axis participates in the hematotoxicity of benzene, and targeting PKM2 has certain therapeutic implications in hematologic diseases.

As a widely used pure elemental carbon in colloidal particles, carbon black was listed as a group 2B carcinogen by IARC in 2010. The most available mechanism information about carbon black and carcinogenesis are from in vivo or in vitro studies. However, few studies concerned the nanoparticle's real-ambient exposure causing systemic change and further affecting the target organ. Herein, we used an ex vivo biosensor assay to investigate the transcriptome change of primary bronchial epithelial cells after treatment with the plasma from workers with long-term occupational carbon black exposure history. Based on ex vivo biosensor assay and transcriptome sequencing, we found the effect of internal systemic environment on epithelial cells after carbon black exposure was an inflammatory response, which mainly activates cell cycle-related pathways. After exposure to carbon black, the internal systemic environment could activate cancer-related pathways like epithelial-mesenchymal transition, hypoxia, TNF-α signaling via NF-κB. The hub genes in the carbon black group (CDC20 and PLK1) and their correlation with the systemic environment were uncovered by constructing the protein-protein interaction network. Inflammatory cytokines, especially CRP, were strongly correlated with the expression of CDC20 and PLK1. Besides, we also find a strong correlation between CDC20 and cytokinesis-block micronucleus endpoints in peripheral blood (rho = 0.591, P < 0.001). Our results show that long-term carbon black exposure might activate cell cycle-related pathways through circulating inflammation and increase the risk of cancer, while the oxidative stress caused by diesel exhaust particles are mainly related to PAHs exposure. After exposure to carbon black, the systemic environment could activate cancer-related pathways like diesel exhaust particles, increasing the risk of lung cancer. These attempts might provide a further understanding of the indirect effect of chronic occupational inhaled carbon black exposure on pulmonary carcinogenesis.

China and the UK use different risk-based approaches to derive soil screening or guideline values (SSVs; SGVs) for contaminants. Here we compare the approaches and the derived values for 6 illustrative contaminants. China’s SSVs are derived using an approach developed in the US as follows: for carcinogens, acceptable level of risk (ACR) is set at 10−6 and the SSVs calculated as 10−6 divided by the soil exposure and toxicity data; for non-carcinogens, the hazard quotient is 1 and the SSV is calculated as 1 divided by the soil exposure and toxicity data. The UK’s SGVs are calculated by the CLEA model, for which the Average Daily Exposure (ADE) from soil sources by a specific exposure route equals the health criteria values (HCVs) for that route, whether for carcinogens or a non-carcinogens. The UK’s CLEA model is also used here to derive SSVs with Chinese input parameters. China’s SSVs, the UK’s SGVs and values for Chinese conditions derived using the UK approach were as follows (mg/kg): As, <1, 35, 20; Cd, 20, 18, 11; Cr (VI), <1, 14, 29; benzene, 1, 1, 2; toluene, 1200, 3005, 3800; ethyl-benzene, 7, 930, 1200. By comparing the differences in toxicity assessment and risk characterization, exposure assessment and parameter types in the methodologies to obtain SSVs in China and the UK, and by combining the CLEA model with Chinese parameterisation, these comparisons highlight that the difference in toxicity assessment and risk characterization methods of carcinogens results in the biggest difference in SSVs between the 2 countries. However, for non-carcinogenic substances, the difference of SSVs calculation method and SSVs is small. The difference in SSVs for carcinogenic substances is also related to the route of exposure. For volatile organic compounds, the presence of indoor respiratory exposure pathways greatly reduces the differences caused by toxicity assessment and risk characterization methods. For non-volatile substances such as heavy metals, the effects of toxicity assessment and risk characterization methods are significant. The SSV of As obtained by the CLEA model with Chinese parameters is closer to the background value of soil in China. In the management of non-volatile contaminated sites such as heavy metals in China, the CLEA model can be used for risk assessment and calculation of site specific SSVs. In the future, China can use the UK method to strengthen its toxicity assessment and risk characterization methods for carcinogenic substances, to reduce the uncertainty in the risk assessment of contaminated sites and improve the scientific management of contaminated sites.

Civilization development is associated with the use of plastic. When plastic was introduced to the market, it was assumed that it was less toxic than glass. Recently, it is known that plastics are serious ecological problem they, do not degrade and remain in the environment for hundreds of years.Plastic may be degraded into micro-particles < 5000 nm in diameter, and further into nanoparticles (NPs) < 100 nm in diameter. NPs have been detected in air, soil, water and sludge.One of the most commonly used plastics is polystyrene (PS) - a product of polymerization of styrene monomers. It is used for the production of styrofoam and other products like toys, CDs and cup covers. In vivo and in vitro studies have suggested that polystyrene nanoparticles (PS-NPs) may penetrate organisms through several routes i.e. skin, respiratory and digestive tracts. They can be deposited in living organisms and accumulate further along the food chain. NPs are surrounded by “protein corona” that allows them penetrating cellular membranes and interacting with cellular structures. Depending on the cell type, NPs may be transported through pinocytosis, phagocytosis, or be transported passively. Currently there are no studies that would indicate a carcinogenic potential of PS-NPs. On the other hand, the PS monomer (styrene) was classified by the International Agency for Research on Cancer (IARC) as a potentially carcinogenic substance (carcinogenicity class B2).Despite of the widespread use of plastics and the presence of plastic NPs of secondary or primary nature, there are no studies that would assess the effect of those substances on human organism. This study was aimed at the review of the literature data concerning the formation of PS-NPs in the environment, their accumulation along the food chain, and their potential adverse effects on organisms on living various organization levels.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been detected in various environmental media and has been implicated as a weak mutagen or carcinogen, but whether TDCIPP can promote the progression of liver tumor remains unclear. In this study, krasⱽ¹² genetically modified zebrafish, Tg(fabp10:rtTA2s-M2; TRE2:EGFP-krasᴳ¹²ⱽ), a model system in which liver tumors can be induced by doxycycline (DOX), was used to evaluate the liver tumor promotion potential of TDCIPP. Briefly, krasⱽ¹² transgenic females were exposed to 0.3 mg/L TDCIPP, 20 mg/L DOX or a binary mixture of 0.3 mg/L TDCIPP with 20 mg/L DOX, and liver size, histopathology, and transcriptional profiles of liver were determined. Treatment with TDCIPP resulted in increased liver size and caused more aggressive hepatocellular carcinoma (HCC). Compared with the exposure to DOX, TDCIPP in the presence of DOX up-regulated the expression of genes relevant with salmonella infection and the toll-like receptor signaling pathway. These results implied an occurrence of inflammatory reaction, which was sustained by the increase in the amount of infiltrated neutrophils in the liver of Tg(lyz:DsRed2) transgenic zebrafish larvae whose neutrophils were labelled by red fluorescent protein under the lysozyme C promoter. Furthermore, compared with the binary exposure of DOX and TDCIPP, treatment with a ternary mixture of TDCIPP, DOX and inflammatory response inhibitor (ketoprofen) significantly decrease the liver size and the amounts of neutrophils in the livers of kras and lyz double transgenic zebrafish larvae. Collectively, our results suggested that TDCIPP could promote the liver tumor progression by induction of hepatic inflammatory responses.

Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are a group of environmental pollutants found in complex mixtures together with PAHs. In contrast to the extensively studied PAHs, which have been established to have mutagenic and carcinogenic properties, much less is known about the effects of oxy-PAHs. The present work aimed to investigate the genotoxic potency of a set of environmentally relevant oxy-PAHs along with environmental soil samples in human bronchial epithelial cells (HBEC). We found that all oxy-PAHs tested induced DNA strand breaks in a dose-dependent manner and some of the oxy-PAHs further induced micronuclei formation. Our results showed weak effects in response to the oxy-PAH containing subfraction of the soil sample. The genotoxic potency was confirmed in both HBEC and HepG2 cells following exposure to oxy-PAHs by an increased level of phospho-Chk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro. We further exposed zebrafish embryos to single oxy-PAHs or a binary mixture with PAH benzo[a]pyrene (B[a]P) and found the mixture to induce comparable or greater effects on the induction of DNA strand breaks compared to the sum of that induced by B[a]P and oxy-PAHs alone. In conclusion, oxy-PAHs were found to elicit genotoxic effects at similar or higher levels to that of B[a]P which indicates that oxy-PAHs may contribute significantly to the total carcinogenic potency of environmental PAH mixtures. This emphasizes further investigations of these compounds as well as the need to include oxy-PAHs in environmental monitoring programs in order to improve health risk assessment.

Homes represent a critical microenvironment in terms of air quality due to the proximity to main particle sources and the lack of proper ventilation systems. Biomass-fed heating systems are still extensively used worldwide, then likely emitting a significant amount of particles in indoor environments. Nonetheless, research on biomass emissions are limited to their effects on outdoor air quality then not properly investigating the emission in indoor environments.To this purpose, the present paper aims to evaluate the exposure to different airborne particle metrics (including both sub- and super-micron particles) and attached carcinogenic compounds in dwellings where three different heating systems were used: open fireplaces, closed fireplaces and pellet stoves. Measurements in terms of particle number, lung-deposited surface area, and PM fraction concentrations were measured during the biomass combustion activities, moreover, PM₁₀ samples were collected and chemically analyzed to obtain mass fractions of carcinogenic compounds attached onto particles. Airborne particle doses received by people exposed in such environments were evaluated as well as their excess lung cancer risk.Most probable surface area extra-doses received by people exposed to open fireplaces on hourly basis (56 mm² h⁻¹) resulted one order of magnitude larger than those experienced for exposure to closed fireplaces and pellet stoves. Lifetime extra risk of Italian people exposed to the heating systems under investigation were larger than the acceptable lifetime risk (10⁻⁵): in particular, the risk due to the open fireplace (8.8 × 10⁻³) was non-negligible when compared to the overall lung cancer risk of typical Italian population.

In the Mediterranean ecosystem, wildfires are very frequent and the predicted future with a probable increase of fires could drastically modify the vegetation scenarios. Vegetation fires are an important source of gases and primary emissions of fine carbonaceous particles in the atmosphere. In this paper, we present gaseous and particulate emissions data from the combustion of different plant tissues (needles/leaves, branches and needle/leaf litter), obtained from one conifer (Pinus halepensis) and one deciduous broadleaf tree (Quercus pubescens). Both species are commonly found throughout the Mediterranean area, often subject to wildfires. Experiments were carried out in a combustion chamber continuously sampling emissions throughout the different phases of a fire (pre-ignition, flaming and smoldering). We identified and quantified 83 volatile organic compounds including important carcinogens that can affect human health. CO and CO₂ were the main gaseous species emitted, benzene and toluene were the dominant aromatic hydrocarbons, methyl-vinyl-ketone and methyl-ethyl-ketone were the most abundant measured oxygenated volatile organic compounds. CO₂ and methane emissions peaked during the flaming phase, while the peak of CO emissions occurred during the smoldering phase. Overall, needle/leaf combustion released a greater amount of volatile organic compounds into the atmosphere than the combustion of branches and litter. There were few differences between emissions from the combustion of the two tree species, except for some compounds. The combustion of P. halepensis released a great amount of monoterpenes as α-pinene, β-pinene, p-cymene, sabinene, 3-carene, terpinolene and camphene that are not emitted from the combustion of Q. pubescens. The combustion of branches showed the longest duration of flaming and peak of temperature. Data presented appear crucial for modeling with the intent of understanding the loss of C during different phases of fire and how different typologies of biomass can affect wildfires and their speciation emissions profile.

Activation of the aryl hydrocarbon receptor (AhR)-mediated activity is one of key events in toxicity of polycyclic aromatic hydrocarbons (PAHs). Although various classes of AhR ligands may differentially activate human and rodent AhR, there is presently a lack of data on the human AhR-inducing relative potencies (REPs) of PAHs. Here, we focused on estimation of the AhR-mediated activities of a large set of environmental PAHs in human gene reporter AZ-AhR cell line, with an aim to develop the human AhR-based REP values with potential implications for risk assessment of PAHs. The previously identified weakly active PAHs mostly failed to activate the AhR in human cells. The order for REPs of individual PAHs in human cells largely corresponded with the available data from rodent-based experimental systems; nevertheless, we identified differences up to one order of magnitude in REP values of PAHs between human and rodent cells. Higher REP values were found in human cells for some important environmental contaminants or suspected carcinogens, such as indeno[1,2,3-cd]pyrene, benz[a]anthracene or benzo[b]fluoranthene, while lower REP values were determined for methyl-substituted PAHs. Our results also indicate that a different rate of metabolism for individual PAHs in human vs. rodent cells may affect estimation of REP values in human cell-based assay, and potentially alter toxicity of some compounds, such as benzofluoranthenes, in humans. We applied the AZ-AhR assay to evaluation of the AhR-mediated activity of complex mixtures of organic compounds associated with diesel exhaust particles, and we identified the polar compounds present in these mixtures as being particularly highly active in human cells, as compared with rodent cells. The present data suggest that differences may exist between the AhR-mediated potencies of PAHs in human and rodent cells, and that the AhR-mediated effects of polar PAH derivatives and metabolites in human cell models deserve further attention.