Benzo[a]pyrene Toxicity Research Articles

Molecular Characteristics of Aberrant Gene Mutations and Expression Profiles Induced by Benzo(a)pyrene in Hepatocellular Carcinoma Cells.

Benzo(a)pyrene (BaP) is a prevalent food and environmental carcinogen. Chronic low-dose BaP exposure can promote the migratory and invasive capacities of human hepatocellular carcinoma (HCC) cells, yet its intricate molecular mechanisms remain elusive. Utilizing the established BaP-exposed HCC cell model, we analyzed the gene expression alteration, exosomal RNA cargo, and genetic variants induced by BaP through transcriptomic and whole-genome sequencing. Transcriptomic analysis revealed significant dysregulation in genes and pathways associated with tumor metastasis, particularly those involved in steroidal lipid metabolism and cell migration. BaP exposure enriched PI3K-AKT, mTOR, and NF-κB signaling pathways and disrupted genes implicated in cellular secretory processes, suggesting the potential involvement of exosomes in metastasis. Exosome analysis depicted the RNA profiling in exosomes of HCC cells altered by BaP, and the exosomal circRNA-miRNA-mRNA interaction network was constructed. Finally, whole-genome sequencing delineated BaP-induced gene mutations and genomic instability in HCC cells. In summary, prolonged low-dose BaP exposure induces intricate molecular alterations in gene mutation and expression profiles in HCC cells, notably those secreted in exosomes, which may potentially remodel the tumor microenvironment and foster HCC metastasis. Our findings offer new insights into the molecular underpinnings of BaP-induced HCC metastasis, thereby advancing the comprehensive understanding of BaP toxicity.

Chronic exposure to environmental concentrations of benzo[a]pyrene causes multifaceted toxic effects of developmental compromise, redox imbalance, and modulated transcriptional profiles in the early life stages of marine medaka (Oryzias melastigma)

Polycyclic aromatic hydrocarbons (PAHs) accumulate and integrate into aquatic environments, raising concerns about the well-being and safety of aquatic ecosystems. Benzo[a]pyrene (BaP), a persistent PAH commonly detected in the environment, has been extensively studied. However, the broader multifaceted toxicity potential of BaP on the early life stages of marine fish during chronic exposure to environmentally relevant concentrations needs further exploration. To fill these knowledge gaps, this study assessed the in vivo biotoxicity of BaP (1, 4, and 8 μg/L) in marine medaka (Oryzias melastigma) during early development over a 30-day exposure period. The investigation included morphological, biochemical, and molecular-level analyses to capture the broader potential of BaP toxicity. Morphological analyses showed that exposure to BaP resulted in skeletal curvatures, heart anomalies, growth retardation, elevated mortality, delayed and reduced hatching rates. Biochemical analyses revealed that BaP exposure not only created oxidative stress but also disrupted the activities of antioxidant enzymes. This disturbance in redox balance was further explored by molecular level investigation. The transcriptional profiles revealed impaired oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle pathways, which potentially inhibited the oxidative respiratory chain in fish following exposure to BaP, and reduced the production of adenosine triphosphate (ATP) and succinate dehydrogenase (SDH). Furthermore, this investigation indicated a potential connection to apoptosis, as demonstrated by fluorescence microscopy and histological analyses, and supported by an increase in the expression levels of related genes via real-time quantitative PCR. This study enhances our understanding of the molecular-level impacts of BaP's multifaceted toxicity in the early life stages of marine medaka, and the associated risks.

Benzo[a]pyrene exposure disrupts the organelle distribution and function of mouse oocytes

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon compound that is generated during combustion processes, and is present in various substances such as foods, tobacco smoke, and burning emissions. BaP is extensively acknowledged as a highly carcinogenic substance to induce multiple forms of cancer, such as lung cancer, skin cancer, and stomach cancer. Recently it is shown to adversely affect the reproductive system. Nevertheless, the potential toxicity of BaP on oocyte quality remains unclear. In this study, we established a BaP exposure model via mouse oral gavage and found that BaP exposure resulted in a notable decrease in the ovarian weight, number of GV oocytes in ovarian, and oocyte maturation competence. BaP exposure caused ribosomal dysfunction, characterized by a decrease in the expression of RPS3 and HPG in oocytes. BaP exposure also caused abnormal distribution of the endoplasmic reticulum (ER) and induced ER stress, as indicated by increased expression of GRP78. Besides, the Golgi apparatus exhibited an abnormal localization pattern, which was confirmed by the GM130 localization. Disruption of vesicle transport processes was observed by the abnormal expression and localization of Rab10. Additionally, an enhanced lysosome and LC3 fluorescence intensity indicated the occurrence of protein degradation in oocytes. In summary, our results suggested that BaP exposure disrupted the distribution and functioning of organelles, consequently affecting the developmental competence of mouse oocytes.

Food emulsifiers increase toxicity of food contaminants in three human GI tract cell lines

Food products simultaneously containing both food contaminants and emulsifiers are common in baked products, coffee and chocolate. Little is known regarding how food contaminants and emulsifiers interact and alter toxicity. Recent studies have shown that while emulsifiers themselves have little toxicity, they could cause changes in the gut microenvironment and lead to issues such as increased uptake of allergens. This study examined toxic effect of two common process contaminants acrylamide (AA) and benzo [a]pyrene (BAP) combined with food emulsifiers polyoxyethylene sorbitan monooleate (TW) or glycerol monostearate (G). In liver cell line HepG2 and gastrointestinal cell lines HIEC6 and Caco-2, toxicities of AA and BAP were increased by TW but not by G as indicated by decrease in IC50 values. Addition of TW also exacerbated gene expression changes caused by AA or BAP. Cellular uptake and cell membrane permeability were enhanced by TW but not by G, but tight junction proteins of Caco-2 monolayer was impacted by both emulsifiers. These results suggested that TW could increase toxicity of AA and BAP through increasing cell permeability thus chemical uptake and potentially through other interactions. The study is to draw the attention of regulators on the potential synergistic interaction of co-occurring chemicals in food.

Determination of soil environment criteria for ecological safety of benzo[a]pyrene in soil based on the species sensitivity distribution approach

Benzo[a]pyrene (BaP) is a highly carcinogenic organic pollutant. Its distinct toxic effects have raised significant concerns among regulators and researchers. However, the absence of established soil environmental criteria for ecological safety of BaP has led to a lack of evidence in the current risk assessment for soil ecological security. To address this gap, we conducted a comprehensive study to investigate the toxicity of BaP using multiple soil organisms, including rice, wheat, lettuce, rape, cucumber, tomato, leonurus, and earthworm. The toxicity data obtained were applied to the species sensitivity distribution (SSD) approach, and the soil environment criteria for ecological safety of BaP under different land use types were derived. The soil environmental criteria for ecological safety of BaP were estimated to be 1.07 (Natural reserve and agricultural land), 1.63 (Parkland), 3.84 (Residential land) and 6.46 (Commercial service and industrial land) mg·kg−1, respectively. This study is the first to conduct toxicity testing and derive soil environmental criteria of BaP in terrestrial ecosystems. These findings are effective supplement for the current soil environmental quality standards and will function as the basis for ecological risk assessment of BaP.

Benzo[a]pyrene represses synaptic vesicle exocytosis by inhibiting P/Q-type calcium channels in hippocampal neurons

Humans are exposed to the common carcinogen benzo[a]pyrene (BaP) by ingesting contaminated foods and water or inhaling polluted air. Given the enriched lipids and reduced antioxidative properties in the brain and the accumulation of BaP in the brain due to its high lipophilicity, the brain is susceptible to BaP-induced toxicity. Exposure to BaP leads to impairments in learning and memory, increased anxiety behavior, and neuronal death. It induces protein dysfunctions in neuronal compartments that play essential roles in neuronal activity or physiology. However, the neurotoxicity of BaP on presynaptic terminals, which is crucial to neurotransmission by releasing synaptic vesicles that contain neurotransmitters, has not yet been investigated. In the present study, we investigated the toxicity of BaP at presynaptic terminals in living hippocampal neurons. These neurons were sourced from transgenic mice pups (postnatal 1-day, a total of 12 pups, equal numbers for each sex) that endogenously express synaptic vesicle-fused pHluorin, which is a green fluorescent protein that enables monitoring of synaptic vesicle dynamics. We observed that BaP suppressed synaptic vesicle exocytosis by inhibiting presynaptic Ca2+ entry via P/Q-type Ca2+ channels. Together with molecular docking simulation, we speculate that BaP and metabolites may bind to the P/Q Ca2+ channels. These results suggest the toxic mechanism of BaP exposure-induced abnormal behavior that provides a basis to evaluate the risk assessment of BaP-induced neurotoxicity.

An integrated method for studying the biodegradation of benzo[a]pyrene by Citrobacter sp. HJS-1 and interaction mechanism based on the structural model of the initial dioxygenase.

A bacterial strain Citrobacter sp. HJS-1 was discovered from the sludge in a drainage canal of a coal mine. Firstly, its biodegradation capacity for benzo[a]pyrene (BaP) was detected under different concentrations. The results proved that the strain possessed excellent biodegradation capacity for BaP with high-efficiency degradation rates ranging from 78.9 to 86.8%. The highest degradation rate was observed in the low-concentration sample, and the high-concentration BaP had a slight influence on the biodegradation capacity due to the potential toxicity of BaP and its oxygen-containing derivatives. Meanwhile, the degradation test for the other five aromatic hydrocarbons (2- to 4-ring) proved that the strain had a comprehensive degradation potential. To clarify the biodegradation mechanism of BaP, a dioxygenase structure was constructed by homology modeling. Then, the interactions between dioxygenase and BaP were researched by molecular simulation. Combined with the identification of the vital BaP-cis-7,8-dihydrodiol intermediate and the interaction analysis, the initial oxidation mode and the binding site of BaP were revealed in the dioxygenase. Taken together, this study has offered a way to understand the biodegradation process of BaP and its interaction mechanism based on experimental and theoretical analysis.

Synergistic toxicity of NiO nanoparticles and benzo[a]pyrene co-exposure in liver cells: Role of free oxygen radicals induced oxidative stress

Current attention has been given on health effects of combined exposure of nanoscale materials and organic pollutants. Nickel (II) oxide nanoparticles (NiO NPs) displays exceptional properties and is being used in various areas such as batteries, diesel–fuel additives, and biomedicals. Benzo[a]pyrene (BaP) is a ubiquitous pollutant. Cigarette smoke, diesel exhaust, and grilled foods are main sources of BaP exposure. Therefore, combined exposure of NiO NPs and BaP to humans is unavoidable. There is a dearth of knowledge on combined effects of NiO NPs and BaP in humans. This study was aimed to investigate co-exposure effects of NiO NPs and BaP in human liver cells (HepG2) and primary rat hepatocytes. We observed that individual and co-exposure of NiO NPs and BaP induced cytotoxicity, lactate dehydrogenase leakage, lipid peroxidation, depletion of mitochondrial membrane potential, and activation of caspases (-3 and -9) in both types of cells. Individual and co-exposure of NiO NPs and BaP further accelerated the generation of free oxygen radicals (reactive oxygen species and hydrogen peroxide) and depletion of antioxidants (glutathione and various antioxidant enzymes). Remarkably, NiO NPs and BaP exerted synergistic toxicity to both HepG2 cells and primary rat hepatocytes. Moreover, combined toxicity of NiO NPs and BaP in both cells was mediated through free oxygen radicals induced oxidative stress. This work warrants further research on risk assessment of co-exposure effects NiO NPs and BaP in an appropriate in vivo model.

Benzo[a]pyrene and a high-fat diet induce aortic injury and promote low-density lipoprotein accumulation in the endothelium

Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant which mainly exposed though diet. High-fat diet (HFD) can induce atherosclerosis, as can BaP. Unhealthy dietary habits lead to high intake of both BaP and lipids. However, the combined effect of BaP and HFD on atherosclerosis and lipid accumulation in the arterial wall, the initial stage of atherosclerosis, is unclear. In this study, C57BL/6 J mice were subchronically exposed to BaP and a HFD, and the mechanism of lipid accumulation was investigated in EA.hy926 and HEK293 cells. Results showed that BaP and HFD increased blood lipids and damaged aortic wall synergistically. Meanwhile, LDL enhanced the toxicity of BaP, and BaP promoted the production of reactive oxygen species and malonaldehyde in EA.hy926 cells, which aggravated LDL-induced cell injury. Moreover, BaP and HFD/LDL induced LDL accumulation in the aortic wall of C57BL/6 J mice/EA.hy926, and the mechanism was by activating AHR/ARNT heterodimer to combine with the scavenger receptor BⅠ (SR-BⅠ) and activin receptor-like kinase 1 (ALK1) promoter regions to transcriptional upregulate its expression, which enhanced the uptake of LDL, and promoting the production of AGEs to inhibit reverse cholesterol transport by SR-BI. BaP and lipid synergistically promoted aortic and endothelial damage, and the health risk of their combined intake should be paid attention to.

Selenium-Enriched Black Soybean Protein Prevents Benzo(a)pyrene-Induced Pyroptotic Colon Damage and Gut Dysbacteriosis.

Selenium-enriched black soybean protein (SeBSP) is a kind of high-quality selenium resource with many physiological functions. Benzo(a)pyrene (BaP) is a well-known injurant that widely exists in high-temperature processed food and has been previously found to cause colon injury. In this study, the effects of SeBSP on colonic damage induced by BaP in BALB/C mice were investigated by comparing it with normal black soybean protein (BSP). SeBSP inhibited the BaP-induced reductions on body weight, food intake, and water intake. Moreover, metabolic enzymes, including AhR, CYP1A1, CYP1B1, and GST-P1, that were promoted by BaP were downregulated by SeBSP, reducing oxidative damage caused by BaP in the metabolic process. The classical pyroptosis indexes (i.e., NLRP3, ASC, Caspase-1, GSDMD) and inflammatory factors (i.e., TNF-α, IL-1β, IL-18, iNOS, COX-2) were downregulated by SeBSP in BaP-treated mice, suggesting the benefits of SeBSP in reducing colonic toxicity. Notably, SeBSP enhanced microbial diversity of gut microbiota and increased relative abundances of prebiotic bacteria, for example, Lactobacillus reuteri, Bacteroides thetaiotaomicron, and genera Bifidobacterium, and Blautia, along with the promotion of short-chain fatty acids. Integrative analysis showed strong links between the antioxidant and anti-inflammatory effects of SeBSP and its altered gut microbiota. Collectively, our study demonstrates the pronounced benefits of Se-enriched black soybean in preventing the colonic toxicity of BaP, and such effects could be mediated by gut microbiota.

Assessment of parental benzo[a]pyrene exposure-induced cross-generational neurotoxicity and changes in offspring sperm DNA methylome in medaka fish.

Previous studies have revealed that DNA methylation changes could serve as potential genomic markers for environmental benzo[a]pyrene (BaP) exposure and intergenerational inheritance of various physiological impairments (e.g. obesity and reproductive pathologies). As a typical aromatic hydrocarbon pollutant, direct BaP exposure has been shown to induce neurotoxicity. To unravel the inheritance mechanisms of the BaP-induced bone phenotype in freshwater medaka, we conducted whole-genome bisulfite sequencing of F1 sperm and identified 776 differentially methylated genes (DMGs). Ingenuity pathway analysis revealed that DMGs were significantly enriched in pathways associated with neuronal development and function. Therefore, it was hypothesized that parental BaP exposure (1 μg/l, 21 days) causes offspring neurotoxicity. Furthermore, the possibility for sperm methylation as an indicator for a neurotoxic phenotype was investigated. The F0 adult brains and F1 larvae were analyzed for BaP-induced direct and inherited toxicity. Acetylcholinesterase activity was significantly reduced in the larvae, together with decreased swimming velocity. Molecular analysis revealed that the marker genes associated with neuron development and growth (alpha1-tubulin, mbp, syn2a, shh, and gap43) as well as brain development (dlx2, otx2, and krox-20) were universally downregulated in the F1 larvae (3 days post-hatching). While parental BaP exposure at an environmentally relevant concentration could induce neurotoxicity in the developing larvae, the brain function of the exposed F0 adults was unaffected. This indicates that developmental neurotoxicity in larvae may result from impaired neuronal development and differentiation, causing delayed brain growth. The present study demonstrates that the possible adverse health effects of BaP in the environment are more extensive than currently understood. Thus, the possibility of multigenerational BaP toxicity should be included in environmental risk assessments.

Evaluation of benzo[a]pyrene-induced toxicity in the estuarine thornfish Therapon jarbua

Our previous study reported that chronic exposure to sublethal levels of estrogen induces DNA damage and endocrine dysfunction in sea bass. In this study, we extended our hypothesis to test changes in genotoxicity and biotransformation induced by Benzo[a]pyrene (BaP) that may regulate endocrine disorders in the estuarine fish. Therapon jarbua an euryhaline fish was exposed to BaP at two different ambient concentrations for 21 days. Biomarkers such as ethoxyresorufin-O-deethlylase (EROD) and DNA damages were assessed in the gill and liver, while neuroendocrine markers such as serotonin (5-HT) and acetyl cholinesterase (AChE) were studied in the brain. The findings showed that longer the exposure, higher the levels of biotransformation enzymes and DNA damage were produced. In both gill and the liver, BaP exposure generated dose-dependent EROD induction and DNA damages, with such a response being more linear in the case of liver than gill. BaP toxicity exacerbated the neurotoxicity by inhibiting acetylcholinesterase (AChE) activity and serotonin levels in the brain and this response was dose-dependent. Neuroendocrine system and biotransformation enzyme have a negative correlation. Results of the correlation and regression data suggest the reduction of endocrine marker might be attributed to the activation of biotransformation enzymes. These findings showed that BaP exposure can harm the gills and liver by inducing the biotransfomation enzyme and causing DNA damage, and so inhibiting neurotransmitters in the brain. These findings are predicted to give fresh insight on the research of the ecotoxicology effect of PAHs on estuarine fish.

Influence of Benzo(a)pyrene on Different Epigenetic Processes.

Epigenetic changes constitute one of the processes that is involved in the mechanisms of carcinogenicity. They include dysregulation of DNA methylation processes, disruption of post-translational patterns of histone modifications, and changes in the composition and/or organization of chromatin. Benzo(a)pyrene (BaP) influences DNA methylation and, depending on its concentrations, as well as the type of cell, tissue and organism it causes hypomethylation or hypermethylation. Moreover, the exposure to polyaromatic hydrocarbons (PAHs), including BaP in tobacco smoke results in an altered methylation status of the offsprings. Researches have indicated a potential relationship between toxicity of BaP and deregulation of the biotin homeostasis pathway that plays an important role in the process of carcinogenesis. Animal studies have shown that parental-induced BaP toxicity can be passed on to the F1 generation as studied on marine medaka (Oryzias melastigma), and the underlying mechanism is likely related to a disturbance in the circadian rhythm. In addition, ancestral exposure of fish to BaP may cause intergenerational osteotoxicity in non-exposed F3 offsprings. Epidemiological studies of lung cancer have indicated that exposure to BaP is associated with changes in methylation levels at 15 CpG; therefore, changes in DNA methylation may be considered as potential mediators of BaP-induced lung cancer. The mechanism of epigenetic changes induced by BaP are mainly due to the formation of CpG-BPDE adducts, between metabolite of BaP—BPDE and CpG, which leads to changes in the level of 5-methylcytosine. BaP also acts through inhibition of DNA methyltransferases activity, as well as by increasing histone deacetylases HDACs, i.e., HDAC2 and HDAC3 activity. The aim of this review is to discuss the mechanism of the epigenetic action of BaP on the basis of the latest publications.

Predicting the in vivo developmental toxicity of benzo[a]pyrene (BaP) in rats by an in vitro\u2013in silico approach

Developmental toxicity testing is an animal-intensive endpoints in toxicity testing and calls for animal-free alternatives. Previous studies showed the applicability of an in vitro–in silico approach for predicting developmental toxicity of a range of compounds, based on data from the mouse embryonic stem cell test (EST) combined with physiologically based kinetic (PBK) modelling facilitated reverse dosimetry. In the current study, the use of this approach for predicting developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) was evaluated, using benzo[a]pyrene (BaP) as a model compound. A rat PBK model of BaP was developed to simulate the kinetics of its main metabolite 3-hydroxybenzo[a]pyrene (3-OHBaP), shown previously to be responsible for the developmental toxicity of BaP. Comparison to in vivo kinetic data showed that the model adequately predicted BaP and 3-OHBaP blood concentrations in the rat. Using this PBK model and reverse dosimetry, a concentration–response curve for 3-OHBaP obtained in the EST was translated into an in vivo dose–response curve for developmental toxicity of BaP in rats upon single or repeated dose exposure. The predicted half maximal effect doses (ED50) amounted to 67 and 45 mg/kg bw being comparable to the ED50 derived from the in vivo dose–response data reported for BaP in the literature, of 29 mg/kg bw. The present study provides a proof of principle of applying this in vitro–in silico approach for evaluating developmental toxicity of BaP and may provide a promising strategy for predicting the developmental toxicity of related PAHs, without the need for extensive animal testing.

Daytime Restricted Feeding Modifies the Temporal Expression of CYP1A1 and Attenuated Damage Induced by Benzo[a]pyrene in Rat Liver When Administered before CYP1A1 Acrophase.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that heterodimerizes with the AhR nuclear translocator (ARNT) to modulate CYP1A1 expression, a gene involved in the biotransformation of benzo[a]pyrene (BaP). The AhR pathway shows daily variations under the control of the circadian timing system. Daytime restricted feeding (DRF) entrains the expression of genes involved in the processing of nutrients and xenobiotics to food availability. Therefore, we evaluate if temporal AhR, ARNT, and CYP1A1 hepatic expression in rats are due to light/dark cycles or fasting/feeding cycles promoted by DRF. Our results show that AhR oscillates throughout the 24 h period in DRF and ad libitum feeding rats (ALF), showing maximum expression at the same time points. DRF modified the peak of ARNT expression at ZT5; meanwhile, ALF animals showed a peak of maximum expression at ZT17. An increased expression of CYP1A1 was linked to the meal time in both groups of animals. Although a high CYP1A1 expression has been previously associated with BaP genotoxicity, our results show that, compared with the ALF group, DRF attenuated the BaP-CYP1A1 induction potency, the liver DNA-BaP adducts, the liver concentration of unmetabolized BaP, and the blood aspartate aminotransferase and alanine aminotransferase activities when BaP is administered prior to the acrophase of CYP1A1 expression. These results demonstrate that DRF modifies the ARNT and CYP1A1 expression and protects from BaP toxicity.

Enzymatic, morphological, and genotoxic effects of benzo[a]pyrene in rainbow trout (Oncorhynchus mykiss).

Fish have defense systems that are capable of repairing damages caused by xenobiotics like benzo[a]pyrene (BaP), so the aims of this study were to identify BaP toxicity in melanomacrophages (MMs) cytoskeleton, evaluate the melanin area in MMs, and analyze genotoxicity. Rainbow trout juveniles (n = 24) were split in 48h and 7d treatments that received 2 mg/kg of BaP. After the experiment, blood samples were collected and liver was removed, to proceed with the analysis: EROD activity, MMs melanin area quantification, melanosomes movements, and a genotoxicity test. The results revealed increased in EROD activity after 48-h and 7-day BaP exposure. The group 7d displayed a reduction in MMs pigmented area, melanosomes aggregation, in addition to an increased frequency of micronucleus. By means of the EROD assay, it was possible to confirm the activation of BaP biotransformation system. The impairment of the melanosomes' movements possibly by an inactivation of the protein responsible for the pigment dispersion consequently affects the melanin area and thus might negatively impact the MMs detoxification capacity. In addition to this cytotoxicity, the increased frequency of micronucleus might also indicate the genotoxicity of BaP in this important fish species.

Molecular toxicity of Benzo(a)pyrene mediated by elicited oxidative stress infer skeletal deformities and apoptosis in embryonic zebrafish

Benzo(a)pyrene (BaP) has become an integral component of disposed of plastic waste, organic pollutants, and remnants of combustible materials in the aquatic environment due to their persistent nature. The accumulation and integration of these polycyclic aromatic hydrocarbons (PAHs) have raised concern to human health and ecological safety. This study assessed the BaP-induced in vivo molecular toxicity with embryonic zebrafish inferred by oxidative stress and apoptosis. BaP was found to induce morphological and physiological abnormalities like delayed hatching (p < 0.05). Computational analysis demonstrated the high-affinity interaction of BaP with the zebrafish hatching enzyme (ZHE1) with Arg, Cys, Ala, Tyr, and Phe located at the active site revealing the influence of BaP on delayed hatching due to alteration of the enzyme structure. RT-PCR analysis revealed significant down-regulation of the skeletal genes Sox9a, SPP1/OPN, and Col1a1 (p < 0.05) genes. The cellular investigations unraveled that the toxicity of BaP extends to the skeletal regions of zebrafish (head, backbone, and tail) because of the elicited oxidative stress leading to apoptosis. The study extended the horizon of understanding of BaP toxicity at the molecular level which will enhance the indulgent and designing of techniques for better ecological sustainability.

Detoxification of Oral Exposure to Benzo(a)pyrene by Lactobacillus plantarum CICC 23121 in Mice.

This study's previous work showed that the carcinogen and mutagen benzo(a)pyrene (BaP) can be adsorbed by Lactobacillus cells in vitro. However, in vivo BaP detoxification by lactic acid bacteria has not yet been investigated. The present study evaluates the effects of orally administered Lactobacillus plantarum CICC 23121 in BaP-treated mice. Oral administration of 50mg kg-1 BaP perturbed the intestinal microflora, caused Proteobacteria to predominate, and severely damaged DNA. However, oral administration of 5 × 1010 CFU mL-1 CICC 23121 in BaP-treated mice enhances fecal BaP excretion from 181.70± 1.04µg/(g∙h) to 271.47± 11.71µg/(g∙h) after 6 h. Fecal BaP excretion reaches up to 280.66± 22.97µg/(g∙h) after the first 4 days of orally administered CICC 23121 and decreased to 94.31± 2.64µg/(g∙h) by day 11. Intestinal microbiota are restored and Firmicutes predominates. CICC 23121 alleviates BaP-induced DNA damage and reduces tail length from 56.37± 5.31 to 39.69± 4.27µm. Therefore, oral CICC23121 consumption is a promising strategy for reducing BaP toxicity in mice. To the best of our knowledge, this report is the first report to demonstrate in vivo that Lactobacillus cells can detoxify BaP.

Benzo[a]pyrene induces fibrotic changes and impairs differentiation in lung stem cells

Human activities have generated air pollution, with extremely small particles (PM 2.5, particulate matter less than 2.5 µm in diameter) and liquid droplets, which become a menace to human health. Among the pollutants, polycyclic aromatic hydrocarbons (PAHs), which enhance the risks of pulmonary dysfunction and cancer development, have been extensively studied. Numerous studies have addressed the effects of PAHs on the respiratory system, whereas the effects on lung stem/progenitor cells remain unknown. Here, we provide evidence that benzo[a]pyrene (BaP), a major toxic PAH, induces fibrotic changes with a loss of α-1,6-fucosylation in CD54+CD157+CD45− cells (lung stem cells). In studies with aryl hydrocarbon receptor (AHR) antagonist, we found that these effects by BaP are independent of the canonical AHR pathway. In addition, these BaP-induced fibrotic changes are reduced by TGF-β antagonist, suggesting an alternative pathway of BaP toxicity is different from other PAH/AHR signaling pathways. Finally, it was observed that BaP impairs the spheroid formation and the podoplanin expression of CD54+CD157+CD45− cells, indicating that BaP suppresses the differentiation of lung stem cells. Taken together, our findings reveal specific BaP-induced injuries in CD54+CD157+CD45− cells.

Co-exposure of Bi2O3 nanoparticles and bezo[a]pyrene-enhanced in vitro cytotoxicity of mouse spermatogonia cells.

Recent attention has been focused on reproductive toxicity of nanoscale materials in combination with pre-existing environmental pollutants. Due to its unique characteristics, bismuth (III) oxide (Bi2O3) nanoparticles (BONPs) are being used in diverse fields including cosmetics and biomedicine. Benzo[a]pyrene (BaP) is a known endocrine disruptor that most common sources of BaP exposure to humans are cigarette smoke and well-cooked barbecued meat. Hence, joint exposure of BONPs and BaP in humans is common. There is scarcity of information on toxicity of BONPs in combination with BaP in human reproductive system. In this work, combined effects of BONPs and BaP in mouse spermatogonia (GC-1 spg) cells were assessed. Results showed that combined exposure of BONPs and BaP synergistically induced cell viability reduction, lactate dehydrogenase leakage, induction of caspases (-3 and -9) and mitochondrial membrane potential loss in GC-1 spg cells. Co-exposure of BONPs and BaP also synergistically induced production of pro-oxidants (reactive oxygen species and hydrogen peroxide) and reduction of antioxidants (glutathione and several antioxidant enzymes). Experiments with N-acetyl-cysteine (NAC, a reactive oxygen species scavenger) indicated that oxidative stress was a plausible mechanism of synergistic toxicity of BONPs and BaP in GC-1 spg cells. Present data could be helpful for future in vivo research and risk assessment of human reproductive system co-exposed to BONPs and BaP.