Early Biological Effects Research Articles

Perspective of low-cost biosensors for genotoxic potential evaluation of urban air

Abstract Background Biosensor technology can potentially revolutionise the area of air pollution monitoring by providing data on early biological effect induction. Such data can be developed for supplementing routine pollution monitoring, improving exposure estimation, including a potential effect estimation and raising community awareness about air pollution. Especially in consideration of complex biological effect such as mutagenic, genotoxic and other proved effects due to the air mixture exposure. The aim of the study is to propose a short-time biosensor for the mutagenic properties evaluation of air pollution. Methods A simple biosensor was developed using genetically modified microorganisms. A first sampling session was conducted in one of the most air-polluted city of Italy using the biosensor and collecting the data of the usual monitoring system, including PM2.5, PM10, NOx, PAHs and metals concentrations. Results The biosensor is able to answer to polluted air mixture indicating a valuable genotoxic effect. Such effect - expressed in relation to the air sampled volume - is comparable to that recorded by traditional genotoxicity in vitro assay on organic extract of particulate matter. Moreover, a comparison with reference measurements is conducted. Repeatability, reproducibility, stability, limit of detection as the impact of environmental factors on biosensor output have been discussed. Conclusions Due to copious difficulties arising when airborne emissions are sampled, biological assays have been applied only sporadically. Aerosol particles are generally collected on a filter and following extraction procedure and bioassay were performed. Monitoring using the biosensor require low sample quantity, directly colliding with the microorganism, and supply good choice when air genotoxicity are to be determined. Key messages Low-cost biosensors can empower high density monitoring of air pollution. The proposed biosensor is able to evaluate genotoxic properties of the air mixture even if data quality is a major concern for its employment.

In utero and childhood exposure to tobacco smoke and multi-layer molecular signatures in children

BackgroundThe adverse health effects of early life exposure to tobacco smoking have been widely reported. In spite of this, the underlying molecular mechanisms of in utero and postnatal exposure to tobacco smoke are only partially understood. Here, we aimed to identify multi-layer molecular signatures associated with exposure to tobacco smoke in these two exposure windows.MethodsWe investigated the associations of maternal smoking during pregnancy and childhood secondhand smoke (SHS) exposure with molecular features measured in 1203 European children (mean age 8.1 years) from the Human Early Life Exposome (HELIX) project. Molecular features, covering 4 layers, included blood DNA methylation and gene and miRNA transcription, plasma proteins, and sera and urinary metabolites.ResultsMaternal smoking during pregnancy was associated with DNA methylation changes at 18 loci in child blood. DNA methylation at 5 of these loci was related to expression of the nearby genes. However, the expression of these genes themselves was only weakly associated with maternal smoking. Conversely, childhood SHS was not associated with blood DNA methylation or transcription patterns, but with reduced levels of several serum metabolites and with increased plasma PAI1 (plasminogen activator inhibitor-1), a protein that inhibits fibrinolysis. Some of the in utero and childhood smoking-related molecular marks showed dose-response trends, with stronger effects with higher dose or longer duration of the exposure.ConclusionIn this first study covering multi-layer molecular features, pregnancy and childhood exposure to tobacco smoke were associated with distinct molecular phenotypes in children. The persistent and dose-dependent changes in the methylome make CpGs good candidates to develop biomarkers of past exposure. Moreover, compared to methylation, the weak association of maternal smoking in pregnancy with gene expression suggests different reversal rates and a methylation-based memory to past exposures. Finally, certain metabolites and protein markers evidenced potential early biological effects of postnatal SHS, such as fibrinolysis.

Formaldehyde Exposure and Epigenetic Effects: A Systematic Review

Formaldehyde (FA) is a general living and occupational pollutant, classified as carcinogenic for humans. Although genotoxicity is recognized as a FA mechanism of action, a potential contribution of epigenetic effects cannot be excluded. Therefore, aim of this review is to comprehensively assess possible epigenetic alterations induced by FA exposure in humans, animals, and cellular models. A systematic review of Pubmed, Scopus, and Isi Web of Science databases was performed. DNA global methylation changes were demonstrated in workers exposed to FA, and also in human bronchial cells. Histone alterations, i.e., the reduction in acetylation of histone lysine residues, in human lung cells were induced by FA. Moreover, a dysregulation of microRNA expression in human lung adenocarcinoma cells as well as in the nose, olfactory bulb and white blood cells of rodents and nonhuman primates was reported. Although preliminary, these findings suggest the role of epigenetic modifications as possible FA mechanisms of action that need deeper qualitative and quantitative investigation. This may allow to define the role of such alterations as indicators of early biological effect and the opportunity to include such information in future risk assessment and management strategies for public and occupationally FA-exposed populations.

Bcl2-induced DNA replication stress promotes lung carcinogenesis in response to space radiation.

Space radiation is characterized by high-linear energy transfer (LET) ionizing radiation. The relationships between the early biological effects of space radiation and the probability of cancer in humans are poorly understood. Bcl2 not only functions as a potent antiapoptotic molecule but also as an oncogenic protein that induces DNA replication stress. To test the role and mechanism of Bcl2 in high-LET space radiation-induced lung carcinogenesis, we created lung-targeting Bcl2 transgenic C57BL/6 mice using the CC10 promoter to drive Bcl2 expression selectively in lung tissues. Intriguingly, lung-targeting transgenic Bcl2 inhibits ribonucleotide reductase activity, reduces dNTP pool size and retards DNA replication fork progression in mouse bronchial epithelial cells. After exposure of mice to space radiation derived from 56iron, 28silicon or protons, the incidence of lung cancer was significantly higher in lung-targeting Bcl2 transgenic mice than in wild-type mice, indicating that Bcl2-induced DNA replication stress promotes lung carcinogenesis in response to space radiation. The findings provide some evidence for the relative effectiveness of space radiation and Bcl-2 at inducing lung cancer in mice.

Micronucleus Frequency in Exfoliated Buccal Cells of Children Living in an Industrialized Area of Apulia (Italy).

Micronuclei (MN) are biomarkers of early biological effect often used for detecting DNA damage in human population exposed to genotoxic agents. The aim of this study was to evaluate the frequency of MN in exfoliated buccal cells of children living in an industrialized (impacted) area compared with that found in children living in a control area without significant anthropogenic impacts. A total of 462 6–8-year-old children (206 in the impacted area, 256 in the control area) attending primary school were enrolled. A questionnaire was administered to the parents of the recruited children to obtain information about personal data, lifestyles, and food habits of their children. Atmospheric particulate fractions were collected near the involved schools to assess the level of environmental exposure of the children. The presence of MN was highlighted in 68.4% of children living in the impacted area with a mean MN frequency of 0.66‰ ± 0.61‰. MN positivity and frequency were significantly lower in the control area (37.1% and 0.27‰ ± 0.43‰, respectively). The frequency of MN was positively associated with quasi-ultrafine particulate matter (PM0.5), traffic near the home, and consuming barbecued food; while adherence to the Mediterranean diet and practicing sport were negatively associated.

Assessment of Radio-Induced Damage in Endothelial Cells Irradiated with 40 kVp, 220 kVp, and 4 MV X-rays by Means of Micro and Nanodosimetric Calculations

The objective of this work was to study the differences in terms of early biological effects that might exist between different X-rays energies by using a mechanistic approach. To this end, radiobiological experiments exposing cell monolayers to three X-ray energies were performed in order to assess the yields of early DNA damage, in particular of double-strand breaks (DSBs). The simulation of these irradiations was set in order to understand the differences in the obtained experimental results. Hence, simulated results in terms of microdosimetric spectra and early DSB induction were analyzed and compared to the experimental data. Human umbilical vein endothelial cells (HUVECs) were irradiated with 40, 220 kVp, and 4 MV X-rays. The Geant4 Monte Carlo simulation toolkit and its extension Geant4-DNA were used for the simulations. Microdosimetric calculations aiming to determine possible differences in the variability of the energy absorbed by the irradiated cell population for those photon spectra were performed on 10,000 endothelial cell nuclei representing a cell monolayer. Nanodosimetric simulations were also carried out using a computation chain that allowed the simulation of physical, physico-chemical, and chemical stages on a single realistic endothelial cell nucleus model including both heterochromatin and euchromatin. DNA damage was scored in terms of yields of prompt DSBs per Gray (Gy) and per giga (109) base pair (Gbp) and DSB complexity was derived in order to be compared to experimental data expressed as numbers of histone variant H2AX (γ-H2AX) foci per cell. The calculated microdosimetric spread in the irradiated cell population was similar when comparing between 40 and 220 kVp X-rays and higher when comparing with 4 MV X-rays. Simulated yields of induced DSB/Gy/Gbp were found to be equivalent to those for 40 and 220 kVp but larger than those for 4 MV, resulting in a relative biological effectiveness (RBE) of 1.3. Additionally, DSB complexity was similar between the considered photon spectra. Simulated results were in good agreement with experimental data obtained by IRSN (Institut de radioprotection et de sûreté nucléaire) radiobiologists. Despite differences in photon energy, few differences were observed when comparing between 40 and 220 kVp X-rays in microdosimetric and nanodosimetric calculations. Nevertheless, variations were observed when comparing between 40/220 kVp and 4 MV X-rays. Thanks to the simulation results, these variations were able to be explained by the differences in the production of secondary electrons with energies below 10 keV.

Urinary 1H NMR metabolomics profile of Italian citizens exposed to background levels of arsenic: a (pre)cautionary tale

Objectives: Arsenic is a toxic metal ubiquitous in the environment and in daily life items. Long-term arsenic exposure is associated with severe adverse health effects involving various target organs. It would be useful to investigate the existence of metabolic alterations associated with lifestyle and/or with the environment. For this purpose, we studied the correlation between urinary arsenic levels and urinary proton nuclear magnetic resonance spectroscopy (1H NMR) metabolomics profiles in a non-occupationally nor environmentally arsenic exposed general population.Methods: Urine samples were collected from 86 healthy subjects. Total and non-alimentary urinary arsenic (U-naAs) levels, namely the sum of arsenite, arsenate, monomethylarsonate and dimethylarsinate, were measured and 1H NMR analysis was performed. Orthogonal Projection to Latent Structures was applied to explore the correlation between the metabolomics profiles and U-naAs levels.Results: Despite the extremely low U-naAs levels (mean value = 6.13 ± 3.17 µg/g creatinine) of our studied population a urinary metabolomics profile related to arsenic was identified.Conclusion: The identified profile could represent a fingerprint of early arsenic biological effect and could be used in further studies as an indicator of susceptibility, also in subjects exposed to a low arsenic dose, with implications in occupational health, toxicology, and public health.

Testing the impact of contaminated sediments from the southeast marine coast of Tunisia on biota: a multibiomarker approach using the flatfish Solea senegalensis.

Coastal marine areas are highly vulnerable to the exposure to various types of stressors and impact of chemical pollution resulting from increasing anthropogenic activities, namely pollution by metals and polycyclic aromatic hydrocarbons (PAHs). To assess ecosystem quality and functions, biomarkers can provide information about the presence and adverse effects of pollutants. Accordingly, the present study was conducted to evaluate the chronic (28 days) biologic effects of putatively contaminated sediments from the Zarzis area, located in the south of the Gulf of Gabes on the Southern Tunisian coast, on the marine flatfish Solea senegalensis. Sediments were collected at three sampling sites, impacted by wastewater discharges, aquaculture activities, and industrial contamination, and then surveyed for metals (Cd, Cu, Cr, Hg, Zn, and Pb) and organic contaminants (polycyclic aromatic hydrocarbons). The quantified biomarkers involved the determination of oxidative stress, phase II metabolism, and the extent of lipid peroxidation (catalase, CAT; glutathione peroxidase activity: total and selenium-dependent, T-GPx and Se-GPx; activities of glutathione-S-transferases, GSTs; levels of lipid peroxidation, by means of the thiobarbituric acid reactive substances assay, TBARS) and neurotoxicity (activity of acetylcholinesterase, AChE). S. senegalensis exposed to potentially contaminated sediments, collected near the aquaculture facility, presented the highest values for the generality of biomarkers tested, and a significant inhibition of AChE activity. A few lesions have been also recorded in the gills and liver tissues of S. senegalensis following chronic exposure. However, the observed lesions in gills (e.g., epithelial lifting, lamellar fusion, gills hyperplasia and hypertrophy, and leukocyte infiltration) and liver (cytoplasmic vacuolation, enlargement of sinusoids, foci of necrosis, and eosinophilic bodies) were of minimal pathological importance and/or low prevalence that did not significantly affect the weighted histopathological indices. Finally, the biological responses evidenced by this flatfish can be potentially caused by metal and PAH pollution occurring in specific areas in the southeast of Tunisia. The type and extent of the observed biochemical alterations strongly suggest that the contaminated sediments from the surveyed areas could cause early adverse biological effects on exposed biota.

Setting up a collaborative European human biological monitoring study on occupational exposure to hexavalent chromium

The EU human biomonitoring initiative, HBM4EU, aims to co-ordinate and advance human biomonitoring (HBM) across Europe. Within its remit, the project is gathering new, policy relevant, EU-wide data on occupational exposure to relevant priority chemicals and developing new approaches for occupational biomonitoring. In this manuscript, the hexavalent chromium [Cr(VI)] study design is presented as the first example of this HBM4EU approach. This study involves eight European countries and plans to recruit 400 workers performing Cr(VI) surface treatment e.g. electroplating or stainless steel welding activities. The aim is to collect new data on current occupational exposure to Cr(VI) in Europe and to test new methods for Cr biomonitoring, specifically the analysis of Cr(VI) in exhaled breath condensate (EBC) and Cr in red blood cells (RBC) in addition to traditional urinary total Cr analyses. Furthermore, exposure data will be complemented with early biological effects data, including genetic and epigenetic effects. Personal air samples and wipe samples are collected in parallel to help informing the biomonitoring results. We present standard operational procedures (SOPs) to support the harmonized methodologies for the collection of occupational hygiene and HBM samples in different countries.

Residential exposure to radon and DNA methylation across the lifecourse: an exploratory study in the ALSPAC birth cohort.

Background: Radon (and its decay products) is a known human carcinogen and the leading cause of lung cancer in never-smokers and the second in ever-smokers. The carcinogenic mechanism from radiation is a combination of genetic and epigenetic processes, but compared to the genetic mechanisms, epigenetic processes remain understudied in humans. This study aimed to explore associations between residential radon exposure and DNA methylation in the general population. Methods: Potential residential radon exposure for 75-metre area buffers was linked to genome-wide DNA methylation measured in peripheral blood from children and mothers of the Accessible Resource for Integrated Epigenomic Studies subsample of the ALSPAC birth cohort. Associations with DNA methylation were tested at over 450,000 CpG sites at ages 0, 7 and 17 years (children) and antenatally and during middle-age (mothers). Analyses were adjusted for potential residential and lifestyle confounding factors and were determined for participants with complete data (n = 786 to 980). Results: Average potential exposure to radon was associated in an exposure-dependent manner with methylation at cg25422346 in mothers during pregnancy, with no associations at middle age. For children, radon potential exposure was associated in an exposure-dependent manner with methylation of cg16451995 at birth, cg01864468 at age 7, and cg04912984, cg16105117, cg23988964, cg04945076, cg08601898, cg16260355 and cg26056703 in adolescence. Conclusions: Residential radon exposure was associated with DNA methylation in an exposure-dependent manner. Although chance and residual confounding cannot be excluded, the identified associations may show biological mechanisms involved in early biological effects from radon exposure.

Residential exposure to radon and DNA methylation across the lifecourse: an exploratory study in the ALSPAC birth cohort

Background: Radon (and its decay products) is a known human carcinogen and the leading cause of lung cancer in never-smokers and the second in ever-smokers. The carcinogenic mechanism from radiation is a combination of genetic and epigenetic processes, but compared to the genetic mechanisms, epigenetic processes remain understudied in humans. This study aimed to explore associations between residential radon exposure and DNA methylation in the general population. Methods: Potential residential radon exposure for 75-metre area buffers was linked to genome-wide DNA methylation measured in peripheral blood from children and mothers of the Accessible Resource for Integrated Epigenomic Studies subsample of the ALSPAC birth cohort. Associations with DNA methylation were tested at over 450,000 CpG sites at ages 0, 7 and 17 years (children) and antenatally and during middle-age (mothers). Analyses were adjusted for potential residential and lifestyle confounding factors and were determined for participants with complete data (n = 786 to 980). Results: Average potential exposure to radon was associated in an exposure-dependent manner with methylation at cg25422346 in mothers during pregnancy, with no associations at middle age. For children, radon potential exposure was associated in an exposure-dependent manner with methylation of cg16451995 at birth, cg01864468 at age 7, and cg04912984, cg16105117, cg23988964, cg04945076, cg08601898, cg16260355 and cg26056703 in adolescence. Conclusions: Residential radon exposure was associated with DNA methylation in an exposure-dependent manner. Although chance and residual confounding cannot be excluded, the identified associations may show biological mechanisms involved in early biological effects from radon exposure.

Human biomonitoring as a tool for exposure assessment in industrially contaminated sites (ICSs). Lessons learned within the ICS and Health European Network.

the mixed and complex nature of industrially contaminated sites (ICSs) leads to heterogeneity in exposure and health risk of residents living nearby. Health, environment, and social aspects are strongly interconnected in ICSs, and local communities are often concerned about potential health impact and needs for remediation. The use of human biomonitoring (HBM) for impact assessment of environmental exposure is increasing in Europe. The COST Action IS1408 on Industrially Contaminated Sites and Health Network (ICSHNet) decided to reflect on the potential and limitations of HBM to assess exposure and early health effects associated with living near ICSs. to discuss challenges and lessons learned for addressing environmental health impact near ICSs with HBM in order to identify needs and priorities for HBM guidelines in European ICSs. based on the experience of the ICSHNet research team, six case studies from different European regions that applied HBM at ICSs were selected. The case studies were systematically compared distinguishing four phases: the preparatory phase; study design; study results; the impact of the results at scientific, societal, and political levels. all six case studies identified opportunities and challenges for applying HBM in ICS studies. A smart choice of (a combination of) sample matrices for biomarker analysis produced information about relevant time-windows of exposure which matched with the activities of the ICSs. Combining biomarkers of exposure with biomarkers of (early) biological effects, data from questionnaires or environmental data enabled fine-tuning of the results and allowed for more targeted remediating actions aimed to reduce exposure. Open and transparent communication of study results with contextual information and involvement of local stakeholders throughout the study helped to build confidence in the study results, gained support for remediating actions, and facilitated sharing of responsibilities. Using HBM in these ICS studies helped in setting priorities in policy actions and in further research. Limitations were the size of the study population, difficulties in recruiting vulnerable target populations, availability of validated biomarkers, and coping with exposure to mixtures of chemicals. based on the identified positive experiences and challenges, the paper concludes with formulating recommendations for a European protocol and guidance document for HBM in ICS. This could advance the use of HBM in local environmental health policy development and evaluation of exposure levels, and promote coordination and collaboration between researchers and risk managers.

Occupational Exposure to Fine Particles and Ultrafine Particles in a Steelmaking Foundry

Several studies have shown an increased mortality rate for different types of tumors, respiratory disease and cardiovascular morbidity associated with foundry work. Airborne particles were investigated in a steelmaking foundry using an electric low-pressure impactor (ELPI+™), a Philips Aerasense Nanotracer and traditional sampling equipment. Determination of metallic elements in the collected particles was carried out by inductively coupled plasma mass spectrometry. The median of ultrafine particle (UFP) concentration was between 4.91 × 103 and 2.33 × 105 part/cm3 (max. 9.48 × 106 part/cm3). Background levels ranged from 1.97 × 104 to 3.83 × 104 part/cm3. Alveolar and deposited tracheobronchial surface area doses ranged from 1.3 × 102 to 8.7 × 103 mm2, and 2.6 × 101 to 1.3 × 103 mm2, respectively. Resulting inhalable and respirable fraction and metallic elements were below limit values set by Italian legislation. A variable concentration of metallic elements was detected in the different fractions of UFPs in relation to the sampling site, the emission source and the size range. This data could be useful in order to increase the knowledge about occupational exposure to fine and ultrafine particles and to design studies aimed to investigate early biological effects associated with the exposure to particulate matter in the foundry industries.

Residential exposure to radon and DNA methylation across the lifecourse: an exploratory study in the ALSPAC birth cohort.

Background: Radon (and its decay products) is a known human carcinogen and the leading cause of lung cancer in never-smokers and the second in ever-smokers. The carcinogenic mechanism from radiation is a combination of genetic and epigenetic processes, but compared to the genetic mechanisms, epigenetic processes remain understudied in humans. This study aimed to explore associations between residential radon exposure and DNA methylation in the general population. Methods: Potential residential radon exposure for 75-metre area buffers was linked to genome-wide DNA methylation measured in peripheral blood from children and mothers of the Accessible Resource for Integrated Epigenomic Studies subsample of the ALSPAC birth cohort. Associations with DNA methylation were tested at over 450,000 CpG sites at ages 0, 7 and 17 years (children) and antenatally and during middle-age (mothers). Analyses were adjusted for potential residential and lifestyle confounding factors and were determined for participants with complete data (n = 786-980). Results: Average potential exposure to radon was associated in an exposure-dependent manner with methylation at cg25422346 in mothers during pregnancy, with no associations at middle age. For children, radon potential exposure was associated in an exposure-dependent manner with methylation of cg16451995 at birth, cg01864468 at age 7, and cg04912984, cg16105117, cg23988964, cg04945076, cg08601898, cg16260355 and cg26056703 in adolescence. Conclusions: Residential radon exposure was associated with DNA methylation in an exposure-dependent manner. Although residual confounding cannot be excluded, the identified associations may show biological mechanisms involved in early biological effects from radon exposure.

The Comet Assay in Human Biomonitoring.

Human biomonitoring studies aim to identify potential exposures to environmental, occupational, or lifestyle toxicants in human populations and are commonly used by public health decision makers to predict disease risk. The Comet assay measures changes in genomic stability and is one of the most reliable biomarkers to indicate early biological effects and therefore accepted by various governmental regulatory agencies. The appeal of the Comet assay lies in its relative simplicity, rapidity, sensitivity, and economic efficiency. Furthermore, the assay is known for its broad versatility, as it can be applied to virtually any human cell and easily adapted in order to detect particular biomarkers of interest, such as DNA repair capacity or single and double-strand breaks. In a standard experiment, isolated single cells are first embedded in agarose, and then lysed in high-salt solutions in order to remove all cellular contents except the DNA attached to a nuclear scaffold. Subsequent electrophoresis results in accumulation of undamaged DNA sequences at the proximity of the nuclear scaffold, while damaged sequences migrate toward the anode. When visualized with fluorochromes, these migrated DNA fragments resemble a Comet tail and can be quantified for their intensity and shape according to internationally drafted guidelines.

Mutagenic and genotoxic effects induced by PM0.5 of different Italian towns in human cells and bacteria: The MAPEC_LIFE study

Particulate matter (PM) is considered an atmospheric pollutant that mostly affects human health. The finest fractions of PM (PM2.5 or less) play a major role in causing chronic diseases.The aim of this study was to investigate the genotoxic effects of PM0.5 collected in five Italian towns using different bioassays. The role of chemical composition on the genotoxicity induced was also evaluated.The present study was included in the multicentre MAPEC_LIFE project, which aimed to evaluate the associations between air pollution exposure and early biological effects in Italian children.PM10 samples were collected in 2 seasons (winter and spring) using a high-volume multistage cascade impactor. The results showed that PM0.5 represents a very high proportion of PM10 (range 10–63%). PM0.5 organic extracts were chemically analysed (PAHs, nitro-PAHs) and tested by the comet assay (A549 and BEAS-2B cells), MN test (A549 cells) and Ames test on Salmonella strains (TA100, TA98, TA98NR and YG1021).The highest concentrations of PAHs and nitro-PAHs in PM0.5 were observed in the Torino, Brescia and Pisa samples in winter. The Ames test showed low mutagenic activity. The highest net revertants/m3 were observed in the Torino and Brescia samples (winter), and the mutagenic effect was associated with PM0.5 (p < 0.01), PAH and nitro-PAH (p < 0.05) concentrations. The YG1021 strain showed the highest sensitivity to PM0.5 samples. No genotoxic effect of PM0.5 extracts was observed using A549 cells except for some samples in winter (comet assay), while BEAS-2B cells showed light DNA damage in the Torino, Brescia and Pisa samples in winter, highlighting the higher sensitivity of BEAS-2B cells, which was consistent with the Ames test (p < 0.01).The results obtained showed that it is important to further investigate the finest fractions of PM, which represent a relevant percentage of PM10, taking into account the chemical composition and the biological effects induced.

Oxidative Stress Index Is Increased in Children of Riverside Towns Affected by Industrial Discharges in Central Mexico and Is Inversely Correlated with Metabolite Excretion of VOC

INTROThe Atoyac River located into Tlaxcala and Puebla states in Mexico, has been classified as highly polluted by environmental authorities, several communities are settled on its banks, affecting around 1.5 million persons, as well as farmland. The river receives waste from industrial discharges, mainly in liquid form, containing a large amount of volatile organic compounds (VOCs), thus giving rise to an environmental distribution of toxics in the area.METHODSTo demonstrate that this environment affects important physiological processes that have an impact in health, we conducted a study of schoolchildren from small communities on the banks of the river and in another similar town located far from it. 91 and 93 students (age range: 8-12, no diagnosed chronic disease), were studied from each site for oxidative stress index (OSI) in blood plasma samples, calculated from the total antioxidant capacity and the total oxidative status, BTEX metabolite excretion in urine samples, and relevant metabolic polymorphisms participating in the bioactivation-detoxification of most VOC: CYP2E1 RsaI, NQO1 C609T, and null polymorphisms of GSTT1 and GSTM1.RESULTSOSI was significantly higher in children living by the river (5.23 &amp;#177; 3.4 vs 2.59 &amp;#177; 1.46, 95% C.I.). At this site, OSI was correlated with diminishing metabolite excretion and a diminished antioxidant capacity; an association with allelic variants of the metabolic polymorphisms of CYP2E1 c2c2, GSTT1 present and NQO1 CC was also observed.CONCLUTIONSThe expected health problems for these children as they grow older involves a widearray of disorders, including cancer and fertility risks for them and their children. Protection programs must be designed that include a constant monitoring of early biological effects, at the same time that environmental protection measures are applied to halt the deterioration of fundamental resources for a healthy life.

Human In Vitro models for respiratory toxicology: evaluation of goblet cell hyperplasia, mucus production, and ciliary beating assays

The health risk of tobacco smoking can best be avoided or reduced by not taking up or quitting the habit. The use of new and innovative tobacco (NTPs, e.g. electronic cigarettes) can either be an aid for smoking cessation or, for those who are not able or willing to quit, an alternative for smoking conventional tobacco products. Before the use of an NTP can be regarded as an effective approach in tobacco harm reduction (THR), the implicated risk has to be evaluated by suitable toxicological methods such as the analysis of the chemical composition as well as assessment of detrimental effects in animal and in vitro studies. In human (clinical) studies, the NTP-related exposure to toxicants and early biological effects can be assessed by the determination of suitable biomarkers. In this review, the suitability of established and newly developed biomarkers of biological effect (BOBEs) for the indicated purpose is evaluated according to five criteria, including the association to diseases, reported difference in BOBE levels between smokers and non-smokers, dose-response relationships, reversibility and kinetics after smoking cessation. Furthermore, the effect size and the resulting sample size required in clinical studies were estimated and considered in the BOBE evaluation process. It is concluded that the rating process presented is useful for selecting BOBEs suitable for risk evaluation of NTPs in clinical and other human studies.

Oxidative stress index is increased in children exposed to industrial discharges and is inversely correlated with metabolite excretion of voc.

children living at polluted sites like this, show early biological effects that might lead to health problems in their adult life. Environmental protection should be enforced to protect people's health in these sites where not even environmental monitoring is done. Environ. Mol. Mutagen. 59:639-652, 2018. © 2018 Wiley Periodicals, Inc.

Imidacloprid Causes DNA Damage in Fish: Clastogenesis as a Mechanism of Genotoxicity.

Neonicotinoids are one of the most widely used insecticides in the world. DNA damage is considered an early biological effect which could lead to reproductive and carcinogenic effects. The present study aimed to evaluate DNA damage and bases oxidation as a mechanism of genotoxicity, on the freshwater fish Australoheros facetus acutely exposed to imidacloprid (IMI). The Comet assay with the nuclease ENDO III enzyme was performed for detecting pyrimidine bases oxidation using blood samples. Micronucleus and other nuclear abnormalities frequencies were also quantified. A significant increase of damage index at 100 and 1000µg/L IMI was detected; while ENDO III score increased from 1 to 1000µg/L IMI; varying both in a linear concentration-response manner. MN frequency increased in fish exposed to 1000µg/L IMI. These results show that short-term exposures to environmentally relevant concentrations of IMI could affect the genetic integrity of fishes through oxidative damage.