Chemical and genotoxic characterization of bioaccessible fractions as a comprehensive in vitro tool in assessing the health risk due to dust-bound contaminant ingestion.

In the last two decades, awareness grew on the matter of the impact of environment on human health. Contaminants sorbed onto soil and settled dust can be ingested and thus represent a hazard, particularly to young children, who play on the ground and bring their hands and objects to their mouth. Metal(loid)s and polycyclic aromatic hydrocarbons (PAHs) are of concern as they are both carcinogenic to humans and ubiquitous in outdoor environments.

Statistical Experimental Design as a New Approach to Optimize a Solid-State Fermentation Substrate for the Production of Spores and Bioactive Compounds from .

Managing organic agricultural wastes is a challenge in today's modern agriculture, where the production of different agricultural goods leads to the generation of large amounts of waste, for example, olive pomace and vine shoot in Mediterranean Europe. The discovery of a cost-effective and environment-friendly way to valorize such types of waste in Mediterranean Europe is encouraged by the European Union regulation. As an opportunity, organic agricultural waste could be used as culture media for solid-state fermentation (SSF) for fungal strains.

Toward an interdisciplinary approach to assess the adverse health effects of dust-containing polycyclic aromatic hydrocarbons (PAHs) and metal(loid)s on preschool children.

Settled dust can function as a pollutant sink for compounds, such as polycyclic aromatic hydrocarbons (PAHs) and metal(loid)s (MMs), which may lead to health issues. Thus, dust represents a hazard specifically for young children, because of their vulnerability and hand-to-mouth behavior favoring dust ingestion. The aim of the present study was to explore the influence of the season and the microenvironment on the concentrations of 15 PAHs and 17 MMs in indoor and outdoor settled dust in three preschools (suburban, urban, and industrial).

Gaining insight into genotoxicity with the comet assay in inhomogenoeous exposure scenarios: The effects of tritiated steel and cement particles on human lung cells in an inhalation perspective.

The comet assay was recently applied for the first time to test the genotoxicity of micrometric stainless steel and cement particles, representative of those produced in the dismantling of nuclear power plants. A large dataset was obtained from in vitro exposure of BEAS-2B lung cells to different concentrations of hydrogenated (non-radiative control) and tritiated particles, to assess the impact of accidental inhalation. Starting from the distributions of the number of nuclei scored at different extent of DNA damage (% tail DNA values), we propose a new comet data treatment designed to consider the inhomogeneity of the action of such particles.

In Vitro Genotoxicity Evaluation of PAHs in Mixtures Using Experimental Design.

Settled dusts are sinks for environmental pollutants, including Polycyclic Aromatic Hydrocarbons (PAHs) that are ubiquitous, persistent, and carcinogenic. To assess their toxicity in mixtures, Toxic Equivalent Factors (TEFs) are routinely used and based on the hypothesis of additive effects, although PAH interactions may occur and remain an open issue. This study investigated genotoxic binary interaction effects for six PAHs in mixtures using two in vitro assays and estimated Genotoxic Equivalent Factors (GEFs) to roughly predict the genotoxicity of PAH in mixtures.

Tritiated Steel Micro-Particles: Computational Dosimetry and Prediction of Radiation-Induced DNA Damage for In Vitro Cell Culture Exposures.

Biological effects of radioactive particles can be experimentally investigated in vitro as a function of particle concentration, specific activity and exposure time. However, a careful dosimetric analysis is needed to elucidate the role of radiation emitted by radioactive products in inducing cyto- and geno-toxicity: the quantification of radiation dose is essential to eventually inform dose-risk correlations. This is even more fundamental when radioactive particles are short-range emitters and when they have a chemical speciation that might further concur to the heterogeneity of energy deposition at the cellular and sub-cellular level.

Cyto-Genotoxicity of Tritiated Stainless Steel and Cement Particles in Human Lung Cell Models.

During the decommissioning of nuclear facilities, the tritiated materials must be removed. These operations generate tritiated steel and cement particles that could be accidentally inhaled by workers. Thus, the consequences of human exposure by inhalation to these particles in terms of radiotoxicology were investigated.

A 3D In Vitro Model of the Human Airway Epithelium Exposed to Tritiated Water: Dosimetric Estimate and Cytotoxic Effects.

Tritium has been receiving worldwide attention, particularly because of its production and use in existing fission reactors and future nuclear fusion technologies, leading to an increased risk of release in the environment. Linking human health effects to low-dose tritium exposures presents a challenge for many reasons. Among these: biological effects strongly depend on the speciation of tritiated products and exposure pathway; large dosimetric uncertainties may exist; measurements using in vitro cell cultures generally lack a description of effects at the tissue level, while large-scale animal studies might be ethically questionable and too highly demanding in terms of resources.

Evaluation of PIG-A-mutated granulocytes and ex-vivo binucleated micronucleated lymphocytes frequencies after breast cancer radiotherapy in humans.

Although the PIG-A gene mutation frequency (MF) is considered a good proxy to evaluate the somatic MF in animals, evidence remains scarce in humans. In this study, a granulocyte PIG-A-mutant assay was evaluated in patients undergoing radiation therapy (RT) for breast cancer. Breast cancer patients undergoing adjuvant RT were prospectively enrolled.

Toxicological Assessment of ITER-Like Tungsten Nanoparticles Using an In Vitro 3D Human Airway Epithelium Model.

The International Thermonuclear Experimental Reactor (ITER) is an international project aimed at the production of carbon-free energy through the use of thermonuclear fusion. During ITER operation, in case of a loss-of-vacuum-accident, tungsten nanoparticles (W-NPs) could potentially be released into the environment and induce occupational exposure via inhalation. W-NPs toxicity was evaluated on MucilAir™, a 3D in vitro cell model of the human airway epithelium.

In Vitro Analysis of the Effects of ITER-Like Tungsten Nanoparticles: Cytotoxicity and Epigenotoxicity in BEAS-2B Cells.

Tungsten was chosen as a wall component to interact with the plasma generated by the International Thermonuclear Experimental fusion Reactor (ITER). Nevertheless, during plasma operation tritiated tungsten nanoparticles (W-NPs) will be formed and potentially released into the environment following a Loss-Of-Vacuum-Accident, causing occupational or accidental exposure. We therefore investigated, in the bronchial human-derived BEAS-2B cell line, the cytotoxic and epigenotoxic effects of two types of ITER-like W-NPs (plasma sputtering or laser ablation), in their pristine, hydrogenated, and tritiated forms.

[The PIG-A gene as a new biomarker of mutagenesis: proof of concept and technical specifications].

Gene mutations are not directly detected by current genotoxicity assays and most of them need a cell culture step. The whole blood PIG-A assay consists in the detection of the mutation frequency within the PIG-A sentinel gene by identification of glycosyl-phosphatidyl-inositol (GPI-) deficient cells. PIG-A mutated/GPI-deficient cells can be detected by flow cytometry as they no longer express surface fluorescence for GPI-linked markers.

Potentially harmful elements in house dust from Estarreja, Portugal: characterization and genotoxicity of the bioaccessible fraction.

Due to their behavioral characteristics, young children are vulnerable to the ingestion of indoor dust, often contaminated with chemicals that are potentially harmful. Exposure to potentially harmful elements (PHEs) is currently exacerbated by their widespread use in several industrial, agricultural, domestic and technological applications. PHEs cause adverse health effects on immune and nervous systems and can lead to cancer development via genotoxic mechanisms.

Poorly soluble cobalt oxide particles trigger genotoxicity via multiple pathways.

Background: Poorly soluble cobalt (II, III) oxide particles (Co3O4P) are believed to induce in vitro cytotoxic effects via a Trojan-horse mechanism. Once internalized into lysosomal and acidic intracellular compartments, Co3O4P slowly release a low amount of cobalt ions (Co(2+)) that impair the viability of in vitro cultures. In this study, we focused on the genotoxic potential of Co3O4P by performing a comprehensive investigation of the DNA damage exerted in BEAS-2B human bronchial epithelial cells.

Antimutagenic potential of harpagoside and Harpagophytum procumbens against 1-nitropyrene.

Background: 1-nitropyrene (1-NPy) is one of the most abundant nitro-polycyclic aromatic hydrocarbons particularly in diesel exhausts. It is a mutagenic and carcinogenic pollutant very widespread in the environment. So the discovery of antimutagenic agents is essential.

Cerium dioxide nanoparticles affect in vitro fertilization in mice.

Due to their catalytic and oxidative properties, cerium dioxide nanoparticles (CeO2NPs) are widely used as diesel additive or as promising therapy in cancerology; yet, scarce data are available on their toxicity, and none on their reproductive toxicity. We showed a significant decrease of fertilization rate, assessed on 1272 oocytes, during in vitro fertilization (IVF) carried out in culture medium containing CeO2NP at very low concentration (0.01 mg.

Ultrastructural interactions and genotoxicity assay of cerium dioxide nanoparticles on mouse oocytes.

Cerium dioxide nanoparticles (C(e)O₂ ENPs) are on the priority list of nanomaterials requiring evaluation. We performed in vitro assays on mature mouse oocytes incubated with C(e)O₂ ENPs to study (1) physicochemical biotransformation of ENPs in culture medium; (2) ultrastructural interactions with follicular cells and oocytes using Transmission Electron Microscopy (TEM); (3) genotoxicity of C(e)O₂ ENPs on follicular cells and oocytes using a comet assay. DNA damage was quantified as Olive Tail Moment.

Detection of environmental clastogens and aneugens in human fibroblasts by cytokinesis-blocked micronucleus assay associated with immunofluorescent staining of CENP-A in micronuclei.

The cytokinesis-blocked micronucleus (CBMN) assay, in combination with fluorescent in situ hybridization (FISH) of human pan-centromeric DNA probes, or with CREST antibodies that specifically stain kinetochore proteins, is widely used on several cell types. It distinguishes micronuclei containing one or several whole chromosomes, which are positively labeled (centromere positive micronucleus, C+MN, due to aneugenic effect), or acentric chromosome fragments, which are unlabeled due to the absence of centromere (centromere negative micronucleus, C-MN, due to clastogenic effect). However, the very slight level of the centromeric signals obtained with the FISH technique on primary human fibroblasts, a cell type commonly used in environmental genetic toxicology, leads to great difficulties in distinguishing C+MN and C-MN.

Biological properties of a neutralized 2.5% sodium hypochlorite solution.

Objectives: The objective of this study was to evaluate the influence of neutralizing a 2.5% NaOCl solution on its cytotoxicity, genotoxicity, and tissue-dissolving potential.

Study Design: The cytotoxicity and the genotoxicity of Dakin, a 2.

[Changes in chromosome number, genetic instability, and occupational exposures].

Aneugenic compounds cause chromosome missegregation during cell division and induce aneuploidy in cells that do not die. Aneuploidy is a key step in the progression from a normal cell into a cancerous cell, and it could represent an early event in the carcinogenic process. Missegregation of chromosome during anaphase often originates from centrosome abnormality, which plays a key role in the formation of the mitotic spindle during cell division.

In vitro interactions between DMSA-coated maghemite nanoparticles and human fibroblasts: A physicochemical and cyto-genotoxical study.

Although the current production of oxide nanoparticles may be modest, the wide range of proposed applications and forecasted growth in production has raised questions about the potential impact of these nanoparticles on the environment and human health. Iron oxide nanoparticles have been proposed for an increasing number of biomedical applications although in vitro toxicity depending on the particles coating has been evidenced. The aim of this study was to examine the potential in vitro cyto- and genotoxicity on human dermal fibroblasts of DMSA-coated maghemite nanoparticles (NmDMSA) as a function of well-defined physicochemical states.

Assessment of occupational exposure to welding fumes by inductively coupled plasma-mass spectroscopy and by the alkaline Comet assay.

Welding fumes are classified as possibly carcinogenic to humans (Group 2B) by the International Agency for Research on Cancer. In the current study, blood and urine concentrations of aluminum (Al), cadmium (Cd), cobalt (Co), chromium (Cr), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) were monitored by inductively coupled plasma-mass spectrometry (ICP-MS) in 30 welders and in 22 controls. In addition, DNA damage was examined in the lymphocytes of these subjects by the alkaline Comet assay.

Okadaic acid: chromosomal non-disjunction analysis in human lymphocytes and study of aneugenic pathway in CHO-K1 cells.

Okadaic acid (OA) is the main marine toxin implicated in the diarrhetic shellfish poisoning (DSP) in humans after consumption of contaminated bivalve molluscs. We have previously shown that OA was an in vitro aneugenic compound that induced chromosome loss via micronuclei formation in CHO-K1 cells. The aims of this study were to investigate the chromosomal non-disjunction (ND) potential of OA in human lymphocytes and the pathways involved for aneuploidy in CHO-K1 cells.

Patterns of gene expressions induced by arsenic trioxide in cultured human fibroblasts.

Arsenic exposure is associated with several human diseases and particularly, with neoplasia. Although the mechanism of arsenic toxicity is not fully understood, several recent works pointed out the involvement of oxidative stress in arsenic-induced DNA damage that, in living cells, correlates with changes in gene expressions. In cultured human fibroblasts exposed for 24 h to micromolar arsenic concentrations, we studied, using real-time RT-PCR, the expression profile of a limited number of genes: genes coding for a stress protein (HSP70), transcription factors (cJUN, cFOS, ETR103, ETR101 and TTP) and cell cycle or DNA repair proteins (P21, GADD153).