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Occupational lead exposure on genome-wide DNA methylation and DNA damage
2022
Meng, Yu | Zhou, Mengyu | Wang, Tuanwei | Zhang, Guanghui | Tu, Yuting | Gong, Shiyang | Zhang, Yunxia | Christiani, David C. | Au, William | Liu, Yun | Xia, Zhao-lin
Lead (Pb) exposure can induce DNA damage and alter DNA methylation but their inter-relationships have not been adequately determined. Our overall aims were to explore such relationships and to evaluate underlying epigenetic mechanisms of Pb-induced genotoxicity in Chinese workers. Blood Pb levels (BLLs) were determined and used as individual's Pb-exposure dose and the Comet assay (i.e., % tail DNA) was conducted to evaluate DNA damage. In the screening assay, 850 K BeadChip sequencing was performed on peripheral blood from 10 controls (BLLs ≤100 μg/L) and 20 exposed workers (i.e., 10 DNA-damaged and 10 DNA-undamaged workers). Using the technique, differentially methylated positions (DMPs) between the controls and the exposed workers were identified. In addition, DMPs were identified between the DNA-undamaged and DNA-damaged workers (% tail DNA >2.14%). In our validation assay, methylation levels of four candidate genes were measured by pyrosequencing in an independent sample set (n = 305), including RRAGC (Ras related GTP binding C), USP1 (Ubiquitin specific protease 1), COPS7B (COP9 signalosome subunit 7 B) and CHEK1 (Checkpoint kinase 1). The result of comparisons between the controls and the Pb-exposed workers show that DMPs were significantly enriched in genes related to nerve conduction and cell cycle. Between DNA-damaged group and DNA-undamaged group, differentially methylated genes were enriched in the pathways related to cell cycle and DNA integrity checkpoints. Additionally, methylation levels of RRAGC and USP1 were negatively associated with BLLs (P < 0.05), and the former mediated 19.40% of the effect of Pb on the % tail DNA. These findings collectively indicated that Pb-induced DNA damage was closely related to methylation of genes in cell cycle regulation, and methylation levels of RRAGC were involved in Pb-induced genotoxicity.
显示更多 [+] 显示较少 [-]Biological toxicity risk assessment of two potential neutral carbon diesel fuel substitutes
2022
Arias, Silvana | Estrada, Verónica | Ortiz, Isabel C. | Molina, Francisco J. | Agudelo, John R.
We investigated the biological response of soluble organic fraction (SOF) and water-soluble fraction (WSF) extracted from particulate matter (PM) emitted by an automotive diesel engine operating in a representative urban driving condition. The engine was fueled with ultra-low sulfur diesel (ULSD), and its binary blends by volume with 13% of butanol (Bu13), and with hydrotreated vegetable oil (HVO) at 13% (HVO13) and 20% (HVO20). Cytotoxicity, genotoxicity, oxidative DNA damage and ecotoxicity tests were carried out, and 16 polycyclic aromatic hydrocarbons (PAH) expressed as tbenzo(a)pyrene total toxicity equivalent (BaP-TEQ) were also analyzed. The Hepatocarcinoma epithelial cell line (HepG2) was exposed to SOF for 24 h and analyzed using comet assay, with the inclusion of formamidopyrimidine DNA glycosylase (FPG) and endonuclease III (Endo III) to recognize oxidized DNA bases. The WSF was evaluated through acute ecotoxicity tests with the aquatic microcrustacean Daphnia pulex (D. Pulex). Results showed that there was no cytotoxic activity for all tested SOF concentrations. Genotoxic responses by all the SOF samples were at same level, except for the HVO13 which was weaker in the absence of the enzymes. The addition of the FPG and Endo III enzymes resulted in a significant increase in the comet tail, indicating that the DNA damage from SOF for all tested fuel blends involves oxidative damage including a higher level of oxidized purines for ULSD and Bu13 in comparison with HVO blends, but the oxidized pyrimidines for HVO blends were slightly higher compared to Bu13. The WSF did not show acute ecotoxicity for any of the fuels. Unlike other samples, Bu13-derived particles significantly increase the BaP-TEQ. The contribution to the genotoxic activity and oxidative DNA from SOF was not correlated to BaP-TEQ, which means that the biological activity of PM might be affected also by other toxic compounds present in particulate phase.
显示更多 [+] 显示较少 [-]TBBPA and its alternative TCBPA induced ROS-dependent mitochondria-mediated apoptosis in the liver of Rana nigromaculata
2022
Jia, Xiuying | Yan, Ruopeng | Lin, Huikang | Liu, Zhiquan | Shen, Lilai | Yang, Hongmei | Wu, Haoying | Shan, Xiaodong | Zhang, Hangjun
Tetrabromobisphenol A (TBBPA), which is the most widely employed brominated flame retardant, and its alternative tetrachlorobisphenol A (TCBPA) are widely distributed in aquatic environments. In the present study, the hepatotoxicity induced by TBBPA and TCBPA was investigated in Rana nigromaculata, and the potential mechanisms were investigated with a particular focus on ROS (reactive oxygen species) -dependent mitochondria-mediated apoptosis. Healthy adult frogs were exposed to 0, 0.001, 0.01, 0.1, and 1 mg/L waterborne TBBPA and TCBPA for 14 days. The results showed that liver weight was significantly increased by 51.52%–98.99% in the 0.01, 0.1, and 1 mg/L TBBPA and TCBPA groups relative to the control. Histological examination revealed that the structure of the liver, to some extent, was influenced by TBBPA and TCBPA with nuclear shrinkage and mitochondrial swelling. Meanwhile, TBBPA and TCBPA have significantly increased the alanine transaminase level in serum and the content of ROS, while inhibiting the activity of superoxide dismutase in the liver. In addition, DNA fragments were observed in the TBBPA and TCBPA groups relative to the control. Expression of Cytochrome C was significantly increased by 1.13-, 1.38-, 1.60-, and 2.46-fold in 0.001, 0.01, 0.1, and 1 mg/L TBBPA, and by 1.26-, 1.51-, 2.14-, and 2.98- fold in 0.001, 0.01, 0.1, and 1 mg/L TCBPA, respectively, which indicated that TCBPA may be more toxic than TBBPA. Similarly, the ratio of Bax/Bcl-2 was increased in a dose-dependent manner. These results indicated that apoptosis in the ROS-dependent mitochondrial pathway mediates hepatotoxicity caused by TBBPA and TCBPA. The present study will facilitate an understanding of the toxicity mechanism of flame retardants.
显示更多 [+] 显示较少 [-]RNA metabarcoding helps reveal zooplankton community response to environmental stressors
2022
Ankley, Phillip J. | Xie, Yuwei | Havens, Sonya | Peters, Lisa | Timlick, Lauren | Rodriguez-Gil, Jose Luis | Giesy, John P. | Palace, Vince P.
DNA metabarcoding can provide a high-throughput and rapid method for characterizing responses of communities to environmental stressors. However, within bulk samples, DNA metabarcoding hardly distinguishes live from the dead organisms. Here, both DNA and RNA metabarcoding were applied and compared in experimental freshwater mesocosms conducted for assessment of ecotoxicological responses of zooplankton communities to remediation treatment until 38 days post oil-spill. Furthermore, a novel indicator of normalized vitality (NV), sequence counts of RNA metabarcoding normalized by that of DNA metabarcoding, was developed for assessment of ecological responses. DNA and RNA metabarcoding detected similar taxa richness and rank of relative abundances. Both DNA and RNA metabarcoding demonstrated slight shifts in measured α-diversities in response to treatments. NV presented relatively greater magnitudes of differential responses of community compositions to treatments compared to DNA or RNA metabarcoding. NV declined from the start of the experiment (3 days pre-spill) to the end (38 days post-spill). NV also differed between Rotifer and Arthropoda, possibly due to differential life histories and sizes of organisms. NV could be a useful indicator for characterizing ecological responses to anthropogenic influence; however, the biology of target organisms and subsequent RNA production need to be considered.
显示更多 [+] 显示较少 [-]Impact of benzo[a]pyrene with other pollutants induce the molecular alternation in the biological system: Existence, detection, and remediation methods
2022
Saravanakumar, Kandasamy | Sivasantosh, Sugavaneswaran | Sathiyaseelan, Anbazhagan | Sankaranarayanan, Alwarappan | Naveen, Kumar Vishven | Zhang, Xin | Jamla, Monica | Vijayasarathy, Sampathkumar | Vishnu Priya, Veeraraghavan | MubarakAli, Davoodbasha | Wang, Myeong-Hyeon
The exposure of benzo [a]pyrene (BaP) in recent times is rather unavoidable than ever before. BaP emissions are sourced majorly from anthropogenic rather than natural provenance from wildfires and volcanic eruptions. A major under-looked source is via the consumption of foods that are deep-fried, grilled, and charcoal smoked foods (meats in particular). BaP being a component of poly aromatic hydrocarbons has been classified as a Group I carcinogenic agent, which has been shown to cause both systemic and localized effects in animal models as well as in humans; has been known to cause various forms of cancer, accelerate neurological disorders, invoke DNA and cellular damage due to the generation of reactive oxygen species and involve in multi-generational phenotypic and genotypic defects. BaP's short and accumulated exposure has been shown in disrupting the fertility of gamete cells. In this review, we have discussed an in-depth and capacious run-through of the various origins of BaP, its economic distribution and its impact as well as toxicological effects on the environment and human health. It also deals with a mechanism as a single compound and its ability to synergize with other chemicals/materials, novel sensitive detection methods, and remediation approaches held in the environment.
显示更多 [+] 显示较少 [-]Legacy metal contamination is reflected in the fish gut microbiome in an urbanised estuary
2022
Suzzi, Alessandra L. | Stat, Michael | MacFarlane, Geoff R. | Seymour, Justin R. | Williams, Nathan LR. | Gaston, Troy F. | Alam, Md Rushna | Huggett, Megan J.
Estuaries are critical habitats subject to a range of stressors requiring effective management. Microbes are gaining recognition as effective environmental indicators, however, the response of host associated communities to stressors remains poorly understood. We examined microbial communities from seawater, sediments and the estuarine fish Pelates sexlineatus, in Australia's largest urbanised estuary, and hypothesised that anthropogenic contamination would be reflected in the microbiology of these sample types. The human faecal markers Lachno3 and HF183 were not detected, indicating negligible influence of sewage, but a gradient in copy numbers of the class 1 integron (intI-1), which is often used as a marker for anthropogenic contamination, was observed in sediments and positively correlated with metal concentrations. While seawater communities were not strongly driven by metal contamination, shifts in the diversity and composition of the fish gut microbiome were observed, with statistical links to levels of metal contamination (F₂, ₂₁ = 1.536, p < 0.01). Within the fish gut microbiome, we further report increased relative abundance of amplicon sequence variants (ASVs; single inferred DNA sequences obtained in sequencing) identified as metal resistant and potentially pathogenic genera, as well as those that may have roles in inflammation. These results demonstrate that microbial communities from distinct habitats within estuarine systems have unique response to stressors, and alterations of the fish gut microbiome may have implications for the adaptation of estuarine fish to legacy metal contamination.
显示更多 [+] 显示较少 [-]How can environmental conditions influence dicofol genotoxicity on the edible Asiatic clam, Meretrix meretrix?
2022
Ivorra, Lucia | Cruzeiro, Catarina | Ramos, Alice | Tagulao, Karen | Cardoso, Patricia G.
Genotoxic effects of dicofol on the edible clam Meretrix meretrix were investigated through a mesocosm experiment. Individuals of M. meretrix, were exposed to environmental concentration (D1 = 50 ng/L) and supra-environmental concentration (D2 = 500 ng/L) of dicofol for 15 days, followed by the same depuration period. DNA damage (i.e., strand breaks and alkali-labile sites) was evaluated at day 1, 7 and 15, during uptake and depuration, using Comet assay (alkaline version) and nuclear abnormalities (NAs) as genotoxicity biomarkers. The protective effects of dicofol against DNA damage induced by ex vivo hydrogen peroxide (H₂O₂) exposure were also assessed. Comet assay results revealed no significant DNA damages under dicofol exposure, indicating 1) apparent lack of genotoxicity of dicofol to the tested conditions and/or 2) resistance of the animals due to optimal adaptation to stress conditions. Moreover, ex vivo H₂O₂ exposure showed an increase in the DNA damage in all the treatments without significant differences between them. However, considering only the DNA damage induced by H₂O₂ during uptake phase, D1 animals had significantly lower DNA damage than those from other treatments, revealing higher protection against a second stressor. NAs data showed a decrease in the % of cells with polymorphic, kidney shape, notched or lobbed nucleus, along the experiment. The combination of these results supports the idea that the clams used in the experiment were probably collected from a stressful environment (in this case Pearl River Delta region) which could have triggered some degree of adaptation to those environmental conditions, explaining the lack of DNA damages and highlighting the importance of organisms’ origin and the conditions that they were exposed during their lives.
显示更多 [+] 显示较少 [-]Bioremediation of PAHs and heavy metals co-contaminated soils: Challenges and enhancement strategies
2022
Ali, Mukhtiar | Song, Xin | Ding, Da | Wang, Qing | Zhang, Zhuanxia | Tang, Zhiwen
Systemic studies on the bioremediation of co-contaminated PAHs and heavy metals are lacking, and this paper provides an in-depth review on the topic. The released sources and transport of co-contaminated PAHs and heavy metals, including their co-occurrence through formation of cation-π interactions and their adsorption in soil are examined. Moreover, it is investigated that co-contamination of PAHs and heavy metals can drive a synergistic positive influence on bioremediation through enhanced secretion of extracellular polymeric substances (EPSs), production of biosynthetic genes, organic acid and enzymatic proliferation. However, PAHs molecular structure, PAHs-heavy metals bioavailability and their interactive cytotoxic effects on microorganisms can exert a challenging influence on the bioremediation under co-contaminated conditions. The fluctuations in bioavailability for microorganisms are associated with soil properties, chemical coordinative interactions, and biological activities under the co-contaminated PAHs-heavy metals conditions. The interactive cytotoxicity caused by the emergence of co-contaminants includes microbial cell disruption, denaturation of DNA and protein structure, and deregulation of antioxidant biological molecules. Finally, this paper presents the emerging strategies to overcome the bioavailability problems and recommends the use of biostimulation and bioaugmentation along with the microbial immobilization for enhanced bioremediation of PAHs-heavy metals co-contaminated sites. Better knowledge of the bioremediation potential is imperative to improve the use of these approaches for the sustainable and cost-effective remediation of PAHs and heavy metals co-contamination in the near future.
显示更多 [+] 显示较少 [-]Cross-sectional and longitudinal relationships between urinary 1-bromopropane metabolite and pulmonary function and underlying role of oxidative damage among urban adults in the Wuhan-Zhuhai cohort in China
2022
Wang, Bin | Fan, Lieyang | Yang, Shijie | Zhou, Min | Mu, Ge | Liu, Wei | Yu, Linling | Yang, Meng | Cheng, Man | Wang, Xing | Qiu, Weihong | Shi, Tingming | Chen, Weihong
1-bromopropane is a US Environmental Protection Agency-identified significant hazardous air pollutant with concerned adverse respiratory effect. We aimed to investigate the relationship between 1-bromopropane exposure and pulmonary function and the underlying role of oxidative damage, which all remain unknown. Pulmonary function and urinary biomarkers of 1-bromopropane exposure (N-Acetyl-S-(n-propyl)-L-cysteine, BPMA) and oxidative damage to DNA (8-hydroxy-deoxyguanosine, 8-OHdG) and lipid (8-iso-prostaglandin-F2α, 8-iso-PGF2α) were measured for 3259 Chinese urban adults from the Wuhan-Zhuhai cohort. The cross-sectional relationship of BPMA with pulmonary function and the joint relationship of BPMA and 8-OHdG or 8-iso-PGF2α with pulmonary function were investigated by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis. Additionally, a panel of 138 subjects was randomly convened from the same cohort to evaluate the stability of BPMA repeatedly measured in urine samples collected over consecutive three days and intervals of one, two, and three years, and to estimate the longitudinal relationship of BPMA with pulmonary function change in three years. We found each 3-fold increase in BPMA was cross-sectionally related to FVC and FEV₁ reductions by 29.88-mL and 25.67-mL, respectively (all P < 0.05). Joint relationship of BPMA and 8-OHdG rather than 8-iso-PGF2α with reduced pulmonary function was observed. Moreover, 8-OHdG significantly mediated 9.44% of the BPMA-related FVC reduction. Findings from the panel revealed a fair to excellent stability (intraclass correlation coefficient: 0.43–0.79) of BPMA in repeated urines collected over a period of three years. Besides, BPMA was longitudinally related to pulmonary function reduction in three years: compared with subjects with persistently low BPMA level, those with persistently high BPMA level had 79.08-mL/year and 49.80-mL/year declines in FVC and FEV₁, respectively (all P < 0.05). Conclusively, 1-bromopropane exposure might impair pulmonary function of urban adult population, and oxidative DNA damage might be a potential mechanism underlying 1-bromopropane impairing pulmonary function especially FVC.
显示更多 [+] 显示较少 [-]Toxicological effects of atenolol and venlafaxine on zebrafish tissues: Bioaccumulation, DNA hypomethylation, and molecular mechanism
2022
Lin, Wenting | Huang, Zhishan | Ping, Senwen | Zhang, Shuan | Wen, Xiufang | He, Yuhe | Ren, Yuan
The beta-blocker atenolol (ATE), and the selective serotonin and norepinephrine reuptake inhibitor, venlafaxine (VEN) are frequently detected in municipal wastewater effluents, but little is known about their ecotoxicological effect on aquatic animals. Herein, ATE and VEN were selected to explore their accumulation and global DNA methylation (GDM) in zebrafish tissues after a 30-day exposure. Molecular dynamics (MD) stimulation was used to investigate the toxic mechanism of ATE and VEN exposure. The results demonstrated that ATE and VEN could reduce the condition factor of zebrafish. The bioaccumulation capacity for ATE and VEN was in the order of liver > gut > gill > brain and liver > gut > brain > gill, respectively. After a 30-day recovery, ATE and VEN could still be detected in zebrafish tissues when exposure concentrations were ≥10 μg/L. Moreover, ATE and VEN induced global DNA hypomethylation in different tissues with a dose-dependent manner and their main target tissues were liver and brain. When the exposure concentrations of ATE and VEN were increased to 100 μg/L, the global DNA hypomethylation of liver and brain were reduced to 27% and 18%, respectively. In the same tissue exposed to the same concentration, DNA hypomethylation induced by VEN was more serious than that of ATE. After a 30-day recovery, the global DNA hypomethylations caused by the two drugs were still persistent, and the recovery of VEN was slower than that of ATE. The MD simulation results showed that both ATE and VEN could reduce the catalytic activity of DNA Methyltransferase 1 (DNMT1), while the effect of VEN on the 3D conformational changes of the DNMT1 domain was more significant, resulting in a lower DNA methylation rate. The current study shed new light on the toxic mechanism and potential adverse impacts of ATE and VEN on zebrafish, providing essential information to the further ecotoxicological risk assessment of these drugs in the aquatic environment.
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