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Gradual effects of gradient concentrations of polystyrene nanoplastics on metabolic processes of the razor clams
2021
Jiang, Qichen | Zhang, Wenyi
With the widespread occurrence and accumulation of plastic waste in the world, plastic pollution has become a serious threat to ecosystem and ecological security, especially to estuarine and coastal areas. Understanding the impacts of changing nanoplastics concentrations on aquatic organisms living in these areas is essential for revealing the ecological effects caused by plastic pollution. In the present study, we revealed the effects of exposure to gradient concentrations (0.005, 0.05, 0.5 and 50 mg/L) of 75 nm polystyrene nanoplastics (PS-NPs) for 48 h on metabolic processes in muscle tissue of a bivalve, the razor clam Sinonovacula constricta, via metabolomic and transcriptomic analysis. Our results showed that PS-NPs caused dose-dependent adverse effects on energy reserves, membrane lipid metabolism, purine metabolism and lysosomal hydrolases. Exposure to PS-NPs reduced energy reserves, especially lipids. Membrane lipid metabolism was sensitive to PS-NPs with contents of phosphocholines (PC), phosphatidylethanolamines (PE) and phosphatidylserines (PS) increasing and degradation being inhibited in all concentrations. High concentrations of PS-NPs altered the purine metabolism via increasing contents of guanosine triphosphate (GTP) and adenine, which may be needed for DNA repair, and consuming inosine and hypoxanthine. During exposure to low concentrations of PS-NPs, lysosomal hydrolases in S. constricta, especially cathepsins, were inhibited while this influence was improved transitorily in 5 mg/L of PS-NPs. These adverse effects together impacted energy metabolism in S. constricta and disturbed energy homeostasis, which was manifested by the low levels of acetyl-CoA in high concentrations of PS-NPs. Overall, our results revealed the effects of acute exposure to gradient concentrations of PS-NPs on S. constricta, especially its metabolic process, and provide perspectives for understanding the toxicity of dynamic plastic pollution to coastal organisms and ecosystem.
Показать больше [+] Меньше [-]Epigenetic silencing of TET1 mediated hydroxymethylation of base excision repair pathway during lung carcinogenesis
2021
Chen, Hong-qiang | Chen, Dong-jiao | Li, Yan | Yuan, Wen-bo | Fan, Jun | Zhang, Zhe | Han, Fei | Jiang, Xiao | Chen, J. P. (Jian-ping) | Wang, Dan-dan | Cao, Jia | Liu, Jin-yi | Liu, Wen-bin
The methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) is an important regulator for the balance of DNA methylation and hydroxymethylation through various pathways. Increasing evidence has suggested that TET1 probably involved in DNA methylation and demethylation dysregulation during chemical carcinogenesis. However, the role and mechanism of TET1 during lung cancer remains unclear. In this study, we found that TET1 expression was significantly down-regulated and the methylation level was significantly up-regulated in 3-methylcholanthrene (3-MCA) induced cell malignant transformation model, rat chemical carcinogenesis model, and human lung cancer tissues. Demethylation experiment further confirmed that DNA methylation negatively regulated TET1 gene expression. TET1 overexpression inhibited cell proliferation, migration and invasion in vitro and in vivo, while knockdown of TET1 resulted in an opposite phenotype. DNA hydroxymethylation level in the promoter region of base excision repair (BER) pathway key genes XRCC1, OGG1, APEX1 significantly decreased and the degree of methylation gradually increased in malignant transformed cells. After differential expression of TET1, the level of hydroxymethylation, methylation and expression of these genes also changed significantly. Furthermore, TET1 binds to XRCC1, OGG1, and APEX1 to maintain them hydroxymethylated. Blockade of BER pathway key gene alone or in combination significantly diminished the effect of TET1. Our study demonstrated for the first time that TET1 expression is regulated by DNA methylation and TET1-mediated hydroxymethylation regulates BER pathway to inhibit the proliferation, migration and invasion during 3-MCA-induced lung carcinogenesis. These results suggested that TET1 gene can be a potential biomarker and therapy target for lung cancer.
Показать больше [+] Меньше [-]Genotoxicity and DNA damage signaling in response to complex mixtures of PAHs in biomass burning particulate matter from cashew nut roasting
2020
Approximately 3 billion people world-wide are exposed to air pollution from biomass burning. Herein, particulate matter (PM) emitted from artisanal cashew nut roasting, an important economic activity worldwide, was investigated. This study focused on: i) chemical characterization of polycyclic aromatic hydrocarbons (PAHs) and oxygenated (oxy-) PAHs; ii) intracellular levels of reactive oxygen species (ROS); iii) genotoxic effects and time- and dose-dependent activation of DNA damage signaling, and iv) differential expression of genes involved in xenobiotic metabolism, inflammation, cell cycle arrest and DNA repair, using A549 lung cells. Among the PAHs, chrysene, benzo[a]pyrene (B[a]P), benzo[b]fluoranthene, and benz[a]anthracene showed the highest concentrations (7.8–10 ng/m³), while benzanthrone and 9,10-anthraquinone were the most abundant oxy-PAHs. Testing of PM extracts was based on B[a]P equivalent doses (B[a]Pₑq). IC₅₀ values for viability were 5.7 and 3.0 nM B[a]Pₑq at 24 h and 48 h, respectively. At these low doses, we observed a time- and dose-dependent increase in intracellular levels of ROS, genotoxicity (DNA strand breaks) and DNA damage signaling (phosphorylation of the protein checkpoint kinase 1 – Chk1). In comparison, effects of B[a]P alone was observed at micromolar range. To our knowledge, no previous study has demonstrated an activation of pChk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro, in lung cells exposed to cashew nut roasting extracts. Sustained induction of expression of several important stress response mediators of xenobiotic metabolism (CYP1A1, CYP1B1), ROS and pro-inflammatory response (IL-8, TNF-α, IL-2, COX2), and DNA damage response (CDKN1A and DDB2) was also identified. In conclusion, our data show high potency of cashew nut roasting PM to induce cellular stress including genotoxicity, and more potently when compared to B[a]P alone. Our study provides new data that will help elucidate the toxic effects of low-levels of PAH mixtures from air PM generated by cashew nut roasting.
Показать больше [+] Меньше [-]Multi-omics response of Pannonibacter phragmitetus BB to hexavalent chromium
2019
Chai, Liyuan | Ding, Chunlian | Li, Jiawei | Yang, Zhihui | Shi, Yan
The release of hexavalent chromium [Cr(VI)] into water bodies poses a major threat to the environment and human health. However, studies of the biological response to Cr(VI) are limited. In this study, a toxic bacterial mechanism of Cr(VI) was investigated using Pannonibacter phragmitetus BB (hereafter BB), which was isolated from chromate slag. The maximum Cr(VI) concentrations with respect to the resistance and reduction by BB are 4000 mg L−1 and 2500 mg L−1, respectively. In the BB genome, more genes responsible for Cr(VI) resistance and reduction are observed compared with other P. phragmitetus strains. A total of 361 proteins were upregulated to respond to Cr(VI) exposure, including enzymes for Cr(VI) uptake, intracellular reduction, ROS detoxification, DNA repair, and Cr(VI) efflux and proteins associated with novel mechanisms involving extracellular reduction mediated by electron transfer, quorum sensing, and chemotaxis. Based on metabolomic analysis, 174 metabolites were identified. Most of the upregulated metabolites are involved in amino acid, glucose, lipid, and energy metabolisms. The results show that Cr(VI) induces metabolite production, while metabolites promote Cr(VI) reduction. Overall, multi-enzyme expression and metabolite production by BB contribute to its high ability to resist/reduce Cr(VI). This study provides details supporting the theory of Cr(VI) reduction and a theoretical basis for the efficient bioremoval of Cr(VI) from the environment.
Показать больше [+] Меньше [-]Bacterial diversity in typical abandoned multi-contaminated nonferrous metal(loid) tailings during natural attenuation
2019
Liu, Jian-li | Yao, Jun | Wang, Fei | Min, Ning | Gu, Ji-hai | Li, Zi-fu | Sunahara, Geoffrey | Duran, Robert | Solevic-Knudsen, Tatjana | Hudson-Edwards, K. A. (Karen A.) | Alakangas, Lena
Abandoned nonferrous metal(loid) tailings sites are anthropogenic, and represent unique and extreme ecological niches for microbial communities. Tailings contain elevated and toxic content of metal(loid)s that had negative effects on local human health and regional ecosystems. Microbial communities in these typical tailings undergoing natural attenuation are often very poorly examined. The diversity and inferred functions of bacterial communities were examined at seven nonferrous metal(loid) tailings sites in Guangxi (China), which were abandoned between 3 and 31 years ago. The acidity of the tailings sites rose over 31 years of site inactivity. Desulfurivibrio, which were always coupled with sulfur/sulfide oxidation to dissimilate the reduction of nitrate/nitrite, were specific in tailings with 3 years abandonment. However, genus beneficial to plant growth (Rhizobium), and iron/sulfur-oxidizing bacteria and metal(loid)-related genera (Acidiferrobacter and Acidithiobacillus) were specific within tailings abandoned for 23 years or more. The increased abundance of acid-generating iron/sulfur-oxidizing and metal(loid)-related bacteria and specific bacterial communities during the natural attenuation could provide new insights for understanding microbial ecosystem functioning in mine tailings. OTUs related to Sulfuriferula, Bacillus, Sulfurifustis, Gaiella, and Thiobacillus genera were the main contributors differentiating the bacterial communities between the different tailing sites. Multiple correlation analyses between bacterial communities and geochemical parameters indicated that pH, TOC, TN, As, Pb, and Cu were the main drivers influencing the bacterial community structures. PICRUSt functional exploration revealed that the main functions were related to DNA repair and recombination, important functions for bacterial adaptation to cope with the multi-contamination of tailings. Such information provides new insights to guide future metagenomic studies for the identification of key functions beyond metal-transformation/resistance. As well, our results offers novel outlooks for the management of bacterial communities during natural attenuation of multi-contaminated nonferrous metal(loid) tailings sites.
Показать больше [+] Меньше [-]Assessment of sperm DNA integrity within the Palaemon longirostris (H. Milne-Edwards, 1837) population of the Seine estuary
2019
Erraud, Alexandre | Bonnard, Marc | Geffard, Olivier | Chaumot, Arnaud | Duflot, Aurélie | Geffard, Alain | Forget-Leray, Joëlle | Xuereb, Benoit
The interpretation of biomarkers in natura should be based on a referential of expected values in uncontaminated conditions. Nevertheless, to build a reference data set of biomarker responses in estuarine areas, which receive chronic pollution loads due to their transition position between continent and sea, is impossible. In this context, the aim of the present work was to propose the use of laboratory recovery period to define a baseline for the measurement of sperm DNA damage by Comet assay in the estuarine prawn Palaemon longirostris. For that, sperm DNA integrity was observed after both a passive (i.e. 20 days in a clean environment) and an active (i.e. forced renewal of spermatophores) recovery of wild P. longirostris specimens from the Seine estuary, in laboratory conditions. Then, the levels of sperm DNA damage recorded within the P. longirostris population of the Seine estuary, during six campaigns of sampling from April 2015 to October 2017, have been interpreted according to the defined threshold values. The results showed a persistence in the level of DNA damage after 20-day in clean environment with the passive recovery. This strategy was inconclusive to reach a baseline level but it revealed the lack of DNA repair mechanisms. For the active recovery, a decrease of 54% of the level of DNA damage has been observed after the first renewal of spermatophores and this level stabilized after the second renewal. On the basis of this second strategy, we defined a mean basal value of sperm DNA damage of 54.9 A.U. and a maximum threshold of 69.7 A.U. (i.e. 95 %CI). The analysis of the results using the reference value highlighted significant abnormal sperm DNA damage within the native population of P. longirostris from the Seine estuary on all stations during the six-sampling campaigns.
Показать больше [+] Меньше [-]Cr(VI)-induced methylation and down-regulation of DNA repair genes and its association with markers of genetic damage in workers and 16HBE cells
2018
Hu, Guiping | Li, Ping | Cui, Xiaoxing | Li, Yang | Zhang, Ji | Zhai, Xinxiao | Yu, Shanfa | Tang, Shichuan | Zhao, Zuchang | Wang, Jing | Jia, Guang
To examine the mechanism of hexavalent chromium [Cr(VI)]-induced carcinogenesis, a cross-sectional study in workers with or without exposure to Cr(VI) as well as in vitro administration of Cr(VI) in 16HBE cells was conducted. We explored the associations between Cr(VI) exposure, methylation modification of DNA repair genes and their expression levels, and genetic damage. Results showed that hypermethylation of CpG sites were observed in both occupationally exposed workers and 16HBE cells administrated Cr(VI). DNA damage markers including 8-hydroxydeoxyguanosine (8-OHdG) and micronucleus frequency in Cr(VI)-exposed workers were significantly higher than the control group. Among workers, blood Cr concentration was positively correlaed with the methylation level of CpG sites in DNA repair genes including CpG6,7, CpG8, CpG9,10,11 of MGMT, CpG11 of HOGG1; CpG15,16,17, CpG19 of RAD51, and genetic damage markers including 8-OHdG and micronucleus frequency. Significant negative association between methylation levels of CpG sites in DNA repair genes and corresponding mRNA was also observed in 16HBE cells. This indicated that Cr(VI) exposure can down-regulate DNA repair gene expression by hypermethylation, which leads to enhanced genetic damage. The methylation level of these CpG sites of DNA repair genes can be potential epigenetic markers for Cr(VI)-induced DNA damage.
Показать больше [+] Меньше [-]Double strand break repair and γ-H2AX formation in erythrocytes of medaka (Oryzias latipes) after γ-irradiation
2017
Sayed, Alaa El-Din Hamid | Igarashi, Kento | Watanabe-Asaka, Tomomi | Mitani, Hiroshi
The study of the DNA damage response in erythrocytes after γ-irradiation may provide evidence for its effectiveness as a biomarkers for genotoxic environmental stress. We previously reported various malformations in erythrocytes of medaka irradiated with10 Gy, but not in their micronuclei. In this study, we optimized an assay method for γ-H2AX and double strand breaks in erythrocytes of adult medaka fish after 15 Gy of γ-irradiation. The highest level of apoptosis and nuclear abnormalities, including in micronuclei, were recorded 4 h after γ-irradiation, as was the highest level of γ-H2AX foci in erythrocytes. These results suggest that recognition and repair processes occur as a response to DNA damage in erythrocytes in medaka.
Показать больше [+] Меньше [-]Associations of polycyclic aromatic hydrocarbons exposure and its interaction with XRCC1 genetic polymorphism with lung cancer: A case-control study
2021
Zhou, Shuang | Zhu, Qiuqi | Liu, Huimin | Jiang, Shunli | Zhang, Xu | Peng, Cheng | Yang, Guanlin | Li, Jiaoyuan | Cheng, Liming | Zhong, Rong | Zeng, Qiang | Miao, Xiaoping | Lü, Qing
Humans are extensively exposed to polycyclic aromatic hydrocarbons (PAHs) daily via multiple pathways. Epidemiological studies have demonstrated that occupational exposure to PAHs increases the risk of lung cancer, but related studies in the general population are limited. Hence, we conducted a case-control study among the Chinese general population to investigate the associations between PAHs exposure and lung cancer risk and analyze the modifications of genetic polymorphisms in DNA repair genes. In this study, we enrolled 122 lung cancer cases and 244 healthy controls in Wuhan, China. Urinary PAHs metabolites were determined by gas chromatography-mass spectrometry, and rs25487 in X-ray repair cross-complementation 1 (XRCC1) gene was genotyped by the Agena Bioscience MassARRAY System. Then, multivariable logistic regression models were performed to estimate the potential associations. We found that urinary hydroxynaphthalene (OH-Nap), hydroxyphenanthrene (OH-Phe) and the sum of hydroxy PAHs (∑OH-PAHs) levels were significantly higher in lung cancer cases than those in controls. After adjusting for gender, age, BMI, smoking status, smoking pack-years, drinking status and family history, urinary ∑OH-Nap and ∑OH-Phe levels were positively associated with lung cancer risk, with dose-response relationships. Compared with those in the lowest tertiles, individuals in the highest tertiles of ∑OH-Nap and ∑OH-Phe had a 2.13-fold (95% CI: 1.10, 4.09) and 2.45-fold (95% CI: 1.23, 4.87) increased risk of lung cancer, respectively. Effects of gender, age, smoking status and smoking pack-years on the associations of PAHs exposure with lung cancer risk were shown in the subgroup analysis. Furthermore, associations of urinary ∑OH-Nap and ∑OH-PAHs levels with lung cancer risk were modified by XRCC1 rs25487 (Pᵢₙₜₑᵣₐcₜᵢₒₙ ≤ 0.025), and were more pronounced in wild-types of rs25487. These findings suggest that environmental exposure to naphthalene and phenanthrene is associated with increased lung cancer risk, and polymorphism of XRCC1 rs25487 might modify the naphthalene exposure-related lung cancer effect.
Показать больше [+] Меньше [-]Physarum polycephalum macroplasmodium exhibits countermeasures against TiO2 nanoparticle toxicity: A physiological, biochemical, transcriptional, and metabolic perspective
2021
Zhang, Zhi | Liang, Zhi Cheng | Liang, Xiu Yi | Zhang, Qing Hai | Wang, Ya Jie | Zhang, Jian Hua | De Liu, Shi
Concerns about the environmental and human health implications of TiO₂ nanoparticles (nTiO₂) are growing with their increased use in consumer and industrial products. Investigations of the underlying molecular mechanisms of nTiO₂ tolerance in organisms will assist in countering nTiO₂ toxicity. In this study, the countermeasures exhibited by the slime mold Physarum polycephalum macroplasmodium against nTiO₂ toxicity were investigated from a physiological, transcriptional, and metabolic perspective. The results suggested that the countermeasures against nTiO₂ exposure include gene-associated metabolic rearrangements in cellular pathways involved in amino acid, carbohydrate, and nucleic acid metabolism. Gene-associated nonmetabolic rearrangements involve processes such as DNA repair, DNA replication, and the cell cycle, and occur mainly when macroplasmodia are exposed to inhibitory doses of nTiO₂. Interestingly, the growth of macroplasmodia and mammal cells was significantly restored by supplementation with a combination of responsive metabolites identified by metabolome analysis. Taken together, we report a novel model organism for the study of nTiO₂ tolerance and provide insights into countermeasures taken by macroplasmodia in response to nTiO₂ toxicity. Furthermore, we also present an approach to mitigate the effects of nTiO₂ toxicity in cells by metabolic intervention.
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