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Environment International Oct 2023Environmental benzo(a)pyrene (BaP) and its ultimate metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) are universal and inevitable persistent organic...
Environmental benzo(a)pyrene (BaP) and its ultimate metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) are universal and inevitable persistent organic pollutants and endocrine disrupting chemicals. Angiogenesis in placental decidua plays a pivotal role in healthy pregnancy. Ferroptosis is a newly identified and iron-dependent cell death mode. However, till now, BaP/BPDE exposure, ferroptosis, defective angiogenesis, and miscarriage have never been correlated; and their regulatory mechanisms have been rarely explored. In this study, we used assays with BPDE-exposed HUVECs (human umbilical vein endothelial cells), decidual tissues and serum samples collected from unexplained recurrent miscarriage and their matched healthy control groups, and placental tissues of BaP-exposed mouse miscarriage model. We found that BaP/BPDE exposure caused ferroptosis and then directly suppressed angiogenesis and eventually induced miscarriage. In mechanism, BaP/BPDE exposure up-regulated free Fe level and promoted lipid peroxidation and also up-regulated MARCHF1 (a novel E3 ligase of GPX4) level to promote the ubiquitination degradation of GPX4, both of which resulted in HUVEC ferroptosis. Furthermore, we also found that GPX4 protein down-regulated the protein levels of VEGFA and ANG-1, two key proteins function for angiogenesis, and thus suppressed HUVEC angiogenesis. In turn, supplement with GPX4 could suppress ferroptosis, recover angiogenesis, and alleviate miscarriage. Moreover, the levels of free Fe and VEGFA in serum might predict the risk of miscarriage. Overall, this study uncovered the crosstalk among BaP/BPDE exposure, ferroptosis, angiogenesis, and miscarriage, discovering novel toxicological effects of BaP/BPDE on human reproductive health. This study also warned the public to avoid exposure to polycyclic aromatic hydrocarbons during pregnancy to effectively prevent adverse pregnancy outcomes.
Topics: Mice; Animals; Pregnancy; Humans; Female; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Ferroptosis; Abortion, Spontaneous; Benzo(a)pyrene; Endothelial Cells; Placenta; Proteins
PubMed: 37802009
DOI: 10.1016/j.envint.2023.108237 -
Free Radical Biology & Medicine Jun 2017The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks... (Review)
Review
The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks during meiotic recombination to generate gamete variety or class switch recombination to create antibody diversity. However, in most cases, genomic damage is potentially harmful to the health of the organism, contributing to disease and aging by promoting deleterious cellular outcomes. A proportion of DNA modifications are caused by exogenous agents, both physical (namely ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene, alkylating agents, platinum compounds and psoralens), which can produce numerous forms of DNA damage, including a range of "simple" and helix-distorting base lesions, abasic sites, crosslinks and various types of phosphodiester strand breaks. More significant in terms of frequency are endogenous mechanisms of modification, which include hydrolytic disintegration of DNA chemical bonds, attack by reactive oxygen species and other byproducts of normal cellular metabolism, or incomplete or necessary enzymatic reactions (such as topoisomerases or repair nucleases). Both exogenous and endogenous mechanisms are associated with a high risk of single strand breakage, either produced directly or generated as intermediates of DNA repair. This review will focus upon the creation, consequences and resolution of single strand breaks, with a particular focus on two major coordinating repair proteins: poly(ADP-ribose) polymerase 1 (PARP1) and X-ray repair cross-complementing protein 1 (XRCC1).
Topics: Animals; Benzopyrenes; DNA Breaks, Single-Stranded; DNA Damage; DNA Repair; Humans; Nervous System Diseases; Poly (ADP-Ribose) Polymerase-1; Radiation, Ionizing; Reactive Oxygen Species; Sunlight; X-ray Repair Cross Complementing Protein 1
PubMed: 27890643
DOI: 10.1016/j.freeradbiomed.2016.11.039 -
IARC Monographs on the Evaluation of... 1989
Review
Topics: Animals; Benzopyrenes; Carcinogens; Chemical Phenomena; Chemistry; Humans; Mice; Mutagens; Risk; Vehicle Emissions
PubMed: 2483416
DOI: No ID Found -
International Journal of Environmental... Oct 2022Occupational exposure as a firefighter is a complex activity that continuously exposes subjects to several health hazards including fire emissions during firefighting.... (Review)
Review
Occupational exposure as a firefighter is a complex activity that continuously exposes subjects to several health hazards including fire emissions during firefighting. Firefighters are exposed to polycyclic aromatic hydrocarbons (PAHs), known as toxic, mutagenic, and carcinogenic compounds, by inhalation, dermal contact, and ingestion. In this work, a literature overview of firefighters' dermal exposure to PAHs after firefighting and data retrieved from skin in vitro/in vivo studies related to their dermal absorption, bioavailability, and associated toxicological and carcinogenic effects are reviewed. The evidence demonstrates the contamination of firefighters' skin with PAHs, mainly on the neck (2.23-62.50 ng/cm), wrists (0.37-8.30 ng/cm), face (2.50-4.82 ng/cm), and hands (1.59-4.69 ng/cm). Concentrations of possible/probable carcinogens (0.82-33.69 ng/cm), including benzopyrene isomers, were found on firefighters' skin. PAHs penetrate the skin tissues, even at low concentrations, by absorption and/or diffusion, and are locally metabolized and distributed by the blood route to other tissues/organs. Lighter PAHs presented increased dermal permeabilities and absorption rates than heavier compounds. Topical PAHs activate the aryl hydrocarbon receptor and promote the enzymatic generation of reactive intermediates that may cause protein and/or DNA adducts. Future research should include in vitro/in vivo assays to perform a more realistic health risk assessment and to explore the contribution of dermal exposure to PAHs total internal dose.
Topics: Air Pollutants, Occupational; Benzopyrenes; Biological Availability; Carcinogens; DNA Adducts; Environmental Monitoring; Firefighters; Humans; Occupational Exposure; Polycyclic Aromatic Hydrocarbons; Receptors, Aryl Hydrocarbon
PubMed: 36231977
DOI: 10.3390/ijerph191912677 -
Systems Biology in Reproductive Medicine Apr 2010Stress causes decreased cell accumulation in early periimplantation embryos and the placental trophoblast stem cells derived from them. Benzopyrene and many other... (Review)
Review
Stress causes decreased cell accumulation in early periimplantation embryos and the placental trophoblast stem cells derived from them. Benzopyrene and many other stressors activate stress enzymes that lead to suppressed stem cell accumulation through diminished proliferation and increased apoptosis. Trophoblast stem cells proliferate and a subpopulation of early postimplantation trophoblast cells differentiate to produce the first placental hormones that arise in the implanting conceptus. These hormones mediate antiluteolytic effects that enable the continuation of a successful implantation. The normal determination and differentiation of placental trophoblast stem cells is dependent upon a series of transcription factors. But, these transcription factors can also be modulated by stress through the activity of stress enzymes. This review enumerates and analyzes recent reports on the effects of benzopyrene on placental function in terms of the emerging paradigm that placental differentiation from stem cells can be regulated when insufficient production of stem cells is caused by stress. In addition, we review the other effects caused by benzopyrene throughout placental development.
Topics: Animals; Benzopyrenes; Blastocyst; Cell Differentiation; Cell Lineage; Embryo Implantation; Female; Humans; Placenta; Pregnancy; Smoking; Stem Cells; Stress, Physiological; Transcription Factors; Trophoblasts
PubMed: 20377314
DOI: 10.3109/19396360903431638 -
International Journal of Environmental... Jan 2023The aim of this study was to analyse the quality of indoor air in sport facilities in one of the sport centres in Poland with respect to microclimatic parameters...
The aim of this study was to analyse the quality of indoor air in sport facilities in one of the sport centres in Poland with respect to microclimatic parameters (temperature, humidity, and air flow velocity), particulate matter concentrations (PM10, PM4, PM2.5, and PM1), gas concentrations (oxygen, ozone, hydrogen sulphide, sulphur dioxide, volatile organic compounds, and benzopyrene), and microbial contamination (the total number of bacteria, specifically staphylococci, including Staphylococcus aureus, haemolytic bacteria, Enterobacteriaceae, Pseudomonas fluorescens, actinomycetes, and the total number of fungi and xerophilic fungi). Measurements were made three times in May 2022 at 28 sampling points in 5 different sporting areas (the climbing wall, swimming pool, swimming pool changing room, and basketball and badminton courts) depending on the time of day (morning or afternoon) and on the outside building. The obtained results were compared with the standards for air quality in sports facilities. The air temperature (21−31 °C) was at the upper limit of thermal comfort, while the air humidity (RH < 40%) in the sports halls in most of the locations was below demanded values. The values for dust pollution in all rooms, except the swimming pool, exceeded the permissible limits, especially in the afternoons. Climatic conditions correlated with a high concentration of dust in the indoor air. Particulate matter concentrations of all fractions exceeded the WHO guidelines in all researched premises; the largest exceedances of standards occurred for PM2.5 (five-fold) and for PM10 (two-fold). There were no exceedances of gaseous pollutant concentrations in the air, except for benzopyrene, which resulted from the influence of the outside air. The total number of bacteria (5.1 × 101−2.0 × 104 CFU m−3) and fungi (3.0 × 101−3.75 × 102 CFU m−3) was exceeded in the changing room and the climbing wall hall. An increased number of staphylococci in the afternoon was associated with a large number of people training. The increased concentration of xerophilic fungi in the air correlated with the high dust content and low air humidity. Along with the increase in the number of users in the afternoon and their activities, the concentration of dust (several times) and microorganisms (1−2 log) in the air increased by several times and 1−2 log, respectively. The present study indicates which air quality parameters should be monitored and provides guidelines on how to increase the comfort of those who practice sports and work in sports facilities.
Topics: Humans; Dust; Air Pollution, Indoor; Particulate Matter; Sulfur Dioxide; Basketball; Benzopyrenes; Air Pollutants; Environmental Monitoring
PubMed: 36674305
DOI: 10.3390/ijerph20021551 -
The Journal of Toxicological Sciences 2022As a widespread environmental pollutant, benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE)-induced neurotoxicity has received increasing attention. Studies have shown that...
As a widespread environmental pollutant, benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE)-induced neurotoxicity has received increasing attention. Studies have shown that BPDE-induced neurodegeneration is due partly to neuronal apoptosis. Unlike apoptosis, ferroptosis is a non-apoptotic form of programmed cell death, but its specific role in the neurotoxicity of BPDE remains unclear. In this work, we investigated the ferroptosis in BPDE-induced cell death in human neuroblastoma cell line SH-SY5Y using a specific pharmacological inhibitor. Lipid peroxides, malondialdehyde production, glutathione / glutathione peroxidase activity, superoxide dismutase activity, and iron content were evaluated. Consistent with previous studies, our data showed that 0.5 μM BPDE poisoning for 24 hr could induce cell apoptosis and that cell survival could be improved by using apoptosis inhibitors. But with prolonged exposure time (72 hr) or increased exposure dose (1.0 μM), we have elucidated and validated that BPDE triggered ferroptosis in human SH-SY5Y cells. We also revealed that suppression of ferroptosis by specific inhibitors, ferrostatin-1 and deferoxamine, significantly rescued the phenotypes of ferroptosis induced by BPDE. BPDE downregulated Nrf2 and its target genes related to redox regulation, GPX4 and SLC7A11, but upregulated HO-1. Our results first demonstrated that BPDE caused cytotoxic effects on cell death via apoptosis and ferroptosis. Most notably, long-term environmental exposure to BPDE becomes a concern due to ferroptosis. Redox imbalance is controlled by the Nrf2, SLC7A11, and HO-1, through which lipid peroxides and ferrous ion accumulation cause ferroptosis after BPDE treatment. These findings highlight that targeting ferroptosis could serve as an effective protective strategy for neurotoxicity of BPDE.
Topics: Humans; Ferroptosis; Benzo(a)pyrene; Epoxy Compounds; NF-E2-Related Factor 2; Lipid Peroxides; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Neuroblastoma; Oxidation-Reduction; Neurotoxicity Syndromes
PubMed: 36450496
DOI: 10.2131/jts.47.519 -
International Journal of Molecular... Jun 2021Polycyclic aromatic hydrocarbons (PAHs) are chemical compounds comprised of carbon and hydrogen molecules in a cyclic arrangement. PAHs are associated with risks to... (Review)
Review
Polycyclic aromatic hydrocarbons (PAHs) are chemical compounds comprised of carbon and hydrogen molecules in a cyclic arrangement. PAHs are associated with risks to human health, especially carcinogenesis. One form of exposure to these compounds is through ingestion of contaminated food, which can occur during preparation and processing involving high temperatures (e.g., grilling, smoking, toasting, roasting, and frying) as well as through PAHs present in the soil, air, and water (i.e., environmental pollution). Differently from changes caused by microbiological characteristics and lipid oxidation, consumers cannot sensorially perceive PAH contamination in food products, thereby hindering their ability to reject these foods. Herein, the occurrence and biological effects of PAHs were comprehensively explored, as well as analytical methods to monitor their levels, legislations, and strategies to reduce their generation in food products. This review updates the current knowledge and addresses recent regulation changes concerning the widespread PAHs contamination in several types of food, often surpassing the concentration limits deemed acceptable by current legislations. Therefore, effective measures involving different food processing strategies are needed to prevent and reduce PAHs contamination, thereby decreasing human exposure and detrimental health effects. Furthermore, gaps in literature have been addressed to provide a basis for future studies.
Topics: Benzopyrenes; Carcinogenesis; Charcoal; Cooking; DNA Adducts; Environmental Pollution; Food; Food Analysis; Food Handling; Humans; Polycyclic Aromatic Hydrocarbons
PubMed: 34199457
DOI: 10.3390/ijms22116010 -
Toxicological Sciences : An Official... Sep 2013Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated during combustion. Dibenzo[def,p]chrysene (DBC) is a high molecular weight...
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated during combustion. Dibenzo[def,p]chrysene (DBC) is a high molecular weight PAH classified as a 2B carcinogen by the International Agency for Research on Cancer. DBC crosses the placenta in exposed mice, causing carcinogenicity in offspring. We present pharmacokinetic data of DBC in pregnant and nonpregnant mice. Pregnant (gestational day 17) and nonpregnant female B6129SF1/J mice were exposed to 15mg/kg DBC by oral gavage. Subgroups of mice were sacrificed up to 48h postdosing, and blood, excreta, and tissues were analyzed for DBC and its major diol and tetrol metabolites. Elevated maximum concentrations and areas under the curve of DBC and its metabolites were observed in blood and tissues of pregnant animals compared with naïve mice. Using a physiologically based pharmacokinetic (PBPK) model, we found observed differences in pharmacokinetics could not be attributed solely to changes in tissue volumes and blood flows that occur during pregnancy. Measurement of enzyme activity in naïve and pregnant mice by activity-based protein profiling indicated a 2- to 10-fold reduction in activities of many of the enzymes relevant to PAH metabolism. Incorporating this reduction into the PBPK model improved model predictions. Concentrations of DBC in fetuses were one to two orders of magnitude below maternal blood concentrations, whereas metabolite concentrations closely resembled those observed in maternal blood.
Topics: Animals; Aryl Hydrocarbon Hydroxylases; Benzopyrenes; Carcinogens; Cytochrome P-450 CYP1B1; Female; Male; Mice; Models, Biological; Pregnancy; Pregnancy, Animal; Tissue Distribution
PubMed: 23744095
DOI: 10.1093/toxsci/kft124 -
Preventive Medicine Mar 1984In 1946, when the causes of lung cancer were much less well understood than they are now, a meeting was held by the British Medical Research Council to review hypotheses... (Comparative Study)
Comparative Study Review
In 1946, when the causes of lung cancer were much less well understood than they are now, a meeting was held by the British Medical Research Council to review hypotheses to explain the remarkable increase in the death rates from lung cancer and to determine strategy. Stocks came away from the meeting to study the community aspects of air pollution, which he did by extending his series of correlation studies, Kennaway to conduct studies of carcinogens in the air, and Hill to carry out a study of smoking in relation to lung cancer. It is now known, of course, that cigarette smoking is by far the most important cause of lung cancer and that about a dozen occupational exposures are also established as causes of this disease. There has been continuing uncertainty about the role of general air pollution. During the past few years, this uncertainty has been compounded with anxiety that the increasing use of diesel-powered vehicles might lead to a deterioration in air quality and, with it, an increase in the incidence of lung cancer. The purpose of this paper is to assess the current role of air pollution as a factor in lung cancer and specifically the contribution of diesel exhaust emissions to the incidence of that disease.
Topics: Adult; Aged; Air Pollutants; Air Pollutants, Occupational; Benzene; Benzopyrenes; Coal; Female; Humans; Lung Neoplasms; Male; Middle Aged; Smoking; Tobacco Smoke Pollution; United Kingdom; United States; Vehicle Emissions
PubMed: 6204329
DOI: 10.1016/0091-7435(84)90052-5