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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 [-]Toxicity assessment of historical aqueous film-forming foams (AFFFs) using cell-based assays
2022
Ojo, Atinuke F. | Peng, Cheng | Annamalai, Prasath | Megharaj, Mallavarapu | Ng, J. (Jack)
Aqueous film-forming foam (AFFF) has historically contained high concentrations of long-chain per-and polyfluoroalkyl substances (PFAS), which have been linked with adverse health outcomes. However, the toxicity of historical AFFFs remains largely unknown, presenting uncertainties in their risk assessment. This study assessed the toxicity of historical AFFFs by exposing human liver cells (HepG2) to various dilutions of 3M Light Water AFFF or Ansulite AFFF (0.001%, 0.002%, 0.005%, 0.009%, 0.019%, 0.038%, 0.075%, 0.15%, and 0.3%) for 24 h. The effects of the two AFFF formulations on the cell viability, intracellular reactive oxygen species (ROS) production, Nrf2-ARE activity, and DNA damage were assessed by CellTiter 96® Aqᵤₑₒᵤₛ One Solution Cell Proliferation Assay (MTS kit), dichlorofluorescein diacetate assay, luciferase assay, and alkaline Comet assay, respectively. The results revealed that the two brands of AFFFs tested were toxic to HepG2 cells at dilutions lower than the recommended 3% application formulation. Specifically, exposure to 3M Light Water AFFF or Ansulite AFFF induced a dilution-dependent decrease in cell viability, increased intracellular ROS production, and increased Nrf2-ARE activity. However, except for the highest concentration (lowest dilution) of 3M Light Water AFFF tested (0.038%.), both 3M Light Water AFFF and Ansulite AFFF did not significantly induce cellular DNA damage. Overall, 3M Light Water AFFF was more toxic than Ansulite AFFF. The findings from this study provided valuable in vitro toxicity data that may better inform the health risk assessment of these historical AFFFs.
显示更多 [+] 显示较少 [-]Biochemical and cellular responses of the freshwater mussel, Hyriopsis bialata, to the herbicide atrazine
2022
Nuchan, Pattanan | Kovitvadhi, Uthaiwan | Sangsawang, Akkarasiri | Kovitvadhi, Satit | Klaimala, Pakasinee | Srakaew, Nopparat
The present study aimed to evaluate biochemical and cellular responses of the freshwater mussel, Hyriopsis bialata, to the herbicide atrazine (ATZ). The mussels were exposed to environmentally-relevant concentrations of ATZ (0, 0.02 and 0.2 mg/L) and a high concentration (2 mg/L) for 0, 7, 14, 21 and 28 days. Tissues comprising male and female gonads, digestive glands and gills were collected and assessed for ethoxyresorufin-O-deethylase (EROD) activity, glutathione S-transferase (GST) activity, multixenobiotic resistance mechanism (MXR), histopathological responses, DNA fragmentation and bioaccumulation of ATZ and its transformation derivatives, desethylatrazine (DEA) and desisopropylatrazine (DIA). Additionally, circulating estradiol levels were determined. It appeared that ATZ did not cause significant changes in activities of EROD, GST and MXR. There were no apparent ATZ-mediated histopathological effects in the tissues, with the exception of the male gonads exhibiting aberrant aggregation of germ cells in the ATZ-treated mussels. Contrarily, ATZ caused significant DNA fragmentation in all tissues of the treated animals in dose- and time-dependent manners. In general, the circulating estradiol levels were higher in the females than in the males. However, ATZ-treated animals did not show significant alterations in the hormonal levels, as compared with those of the untreated animals. Herein, we showed for the first time differentially spatiotemporal distribution patterns of bioaccumulation of ATZ, DEA and DIA, with ATZ and DEA detectable in the gonads of both sexes, DEA and DIA in the digestive glands and only DEA in the gills. The differential distribution patterns of bioaccumulation of ATZ and its derivatives among the tissues point to different pathways and tissue capacity in transforming ATZ into its transformation products. Taken together, the freshwater mussel H. bialata was resistant to ATZ likely due to their effective detoxification. However, using DNA damage as a potential biomarker, H. bialata is a promising candidate for biomonitoring aquatic toxicity.
显示更多 [+] 显示较少 [-]Evaluation of genotoxicity in bat species found on agricultural landscapes of the Cerrado savanna, central Brazil
2022
Habitat loss and fragmentation together represent the most significant threat to the world's biodiversity. In order to guarantee the survival of this diversity, the monitoring of bioindicators can provide important insights into the health of a natural environment. In this context, we used the comet assay and micronucleus test to evaluate the genotoxic susceptibility of 126 bats of eight species captured in soybean and sugarcane plantation areas, together with a control area (conservation unit) in the Cerrado savanna of central Brazil. No significant differences were found between the specimens captured in the sugarcane and control areas in the frequency of micronuclei and DNA damage (comet assay). However, the omnivore Phyllostomus hastatus had a higher frequency of nuclear abnormalities than the frugivore Carollia perspicillata in the sugarcane area. Insectivorous and frugivorous bats presented a higher frequency of genotoxic damage than the nectarivores in the soybean area. In general, DNA damage and micronuclei were significantly more frequent in agricultural environments than in the control area. While agricultural development is an economic necessity in developing countries, the impacts on the natural landscape may result in genotoxic damage to the local fauna, such as bats. Over the medium to long term, then DNA damage may have an increasingly negative impact on the wellbeing of the local species.
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 [-]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 [-]Associations of propylene oxide exposure with fasting plasma glucose and diabetes: Roles of oxidative DNA damage and lipid peroxidation
2022
Liu, Wei | Wang, Bin | Yang, Shijie | Xu, Tao | Yu, Linling | Wang, Xing | Cheng, Man | Zhou, Min | Chen, Weihong
Whether propylene oxide (PO) exposure is associated with hyperglycemia were rarely explored. We aimed to determine the relationship between PO exposure and glucose metabolism, and potential role of oxidative stress. Among 3294 Chinese urban adults, urinary PO metabolite (N-Acetyl-S-(2-hydroxypropyl)-L-cysteine, 2HPMA), biomarkers of oxidative DNA damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) and lipid peroxidation (8-isoprostane, 8-iso-PGF₂α) in urine were determined. The associations of 2HPMA with 8-OHdG, 8-iso-PGF₂α, fasting plasma glucose (FPG), and risk of diabetes were explored. The roles of 8-OHdG and 8-iso-PGF₂α on association of 2HPMA with FPG and risk of diabetes were detected. After adjusted for potential confounders, each 1-unit increase in log-transformed concentration of 2HPMA was associated with a 0.15-mmol/L increase in FPG level, and the adjusted OR (95% CI) of diabetes by the associations of log-transformed urinary 2HPMA concentrations was 1.47 (95% CI: 1.03–2.11). Combination effects of 2HPMA with 8-OHdG or 8-iso-PGF₂α on risk of diabetes were detected, and elevated 8-iso-PGF₂α significantly mediated 34.5% of the urinary 2HPMA-associated FPG elevation. PO exposure was positively associated with FPG levels and risk of diabetes. PO exposure combined with DNA oxidative damage or lipid peroxidation may increase the risk of diabetes, and lipid peroxidation may partially mediate the PO exposure-induced FPG elevation.
显示更多 [+] 显示较少 [-]Genotoxic potential of bisphenol A: A review
2022
Ďurovcová, Ivana | Kyzek, Stanislav | Fabová, Jana | Makuková, Jana | Gálová, Eliška | Ševčovičová, Andrea
Bisphenol A (BPA), as a major component of some plastic products, is abundant environmental pollutant. Due to its ability to bind to several types of estrogen receptors, it can trigger multiple cellular responses, which can contribute to various manifestations at the organism level. The most studied effect of BPA is endocrine disruption, but recently its prooxidative potential has been confirmed. BPA ability to induce oxidative stress through increased ROS production, altered activity of antioxidant enzymes, or accumulation of oxidation products of biomacromolecules is observed in a wide range of organisms – estrogen receptor-positive and -negative. Subsequently, increased intracellular oxidation can lead to DNA damage induction, represented by oxidative damage, single- and double-strand DNA breaks. Importantly, BPA shows several mechanisms of action and can trigger adverse effects on all organisms inhabiting a wide variety of ecosystem types. Therefore, the main aim of this review is to summarize the genotoxic effects of BPA on organisms across all taxa.
显示更多 [+] 显示较少 [-]A review on microplastics and nanoplastics in the environment: Their occurrence, exposure routes, toxic studies, and potential effects on human health
2022
Sangkham, Sarawut | Faikhaw, Orasai | Munkong, Narongsuk | Sakunkoo, Pornpun | Arunlertaree, Chumlong | Chavali, Murthy | Mousazadeh, Milad | Tiwari, Ananda
Microplastics (MPs) and nanoplastics (NPs) are emerging environmental pollutants, having a major ecotoxicological concern to humans and many other biotas, especially aquatic animals. The physical and chemical compositions of MPs majorly determine their ecotoxicological risks. However, comprehensive knowledge about the exposure routes and toxic effects of MPs/NPs on animals and human health is not fully known. Here this review focuses on the potential exposure routes, human health impacts, and toxicity response of MPs/NPs on human health, through reviewing the literature on studies conducted in different in vitro and in vivo experiments on organisms, human cells, and the human experimental exposure models. The current literature review has highlighted ingestion, inhalation, and dermal contacts as major exposure routes of MPs/NPs. Further, oxidative stress, cytotoxicity, DNA damage, inflammation, immune response, neurotoxicity, metabolic disruption, and ultimately affecting digestive systems, immunology, respiratory systems, reproductive systems, and nervous systems, as serious health consequences.
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