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11.
Cytochrome P450s (CYPs) play a key role in the metabolism of a wide range of environmental xenobiotics and endogenous compounds. The expression and activity levels of CYPs can be elevated by a process of induction involving the activation of nuclear receptors. The effects of the ionic liquid 1-octyl-3-methylimidazolium chloride ([C8mim][Cl]) on the expression of cytochrome P450 members, including CYP1A1, CYP2E1, and CYP3A, as well as on aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) in mouse mammary carcinoma cells (EMT6) were investigated by using quantitative real-time PCR in the present study. The results reveal that [C8mim][Cl]-exposure up-regulates the expressions of CYP1A1, CYP2E1, and CYP3A at mRNA level, suggesting that imidazolium-based ionic liquids can activate CYPs. Our results also suggest that [C8mim][Cl]-mediated CYP3A induction be PXR-dependent. This result may be beneficial to evaluating the environmental toxicity of imidazolium-based ionic liquids and investigating the metabolism of imidazolium-derivative drugs. 相似文献
12.
Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) are ubiquitous contaminants and can be considerably accumulated by natural plants. In order to elucidate the biochemical and physiological responses of plant to PCDD/Fs, tobacco Bright Yellow-2 (BY-2) cells were selected as model plant and treated with time- and concentration-dependent PCDD/Fs. The toxic effect and oxidative stress caused by PCDD/Fs were evident, which could be indicted by the reduction in fresh mass, the increase in malondialdehyde (MDA) content, and the damage of tobacco cell ultrastructure. PCDD/Fs tolerance was correlated with changes in antioxidant system and hormones of tobacco cells. Superoxide dismutase (SOD) and peroxidase (POD) exhibited peak enzyme activities at the PCDD/Fs concentration of 1000 ng WHO98-TEQ g−1 fresh weight. Glutathione reductase (GR) enzyme activity increased monotonically at high level PCDD/Fs, but the activity of catalase (CAT) was only slightly affected at all treatment. Meanwhile, the exposure to PCDD/Fs resulted in the changes of hormones content. With the increase of exposure concentration of PCDD/Fs, the levels of indole-3-acetic acid (IAA) and abscisic acid (ABA) increased, whereas the concentration of jasmonates (JAs) decreased. The above results suggest that tobacco cells had the ability to cope with the oxidative stress induced by low concentration of PCDD/Fs through increasing the activities of antioxidant enzymes and alternating plant hormones levels. However, oxidative stress and toxicity would burst out when plant cells were exposed to the high levels of PCDD/Fs. 相似文献
13.
二噁英(代DD)是一类毒性较强的环境污染物质.试验使用印记法定量检测了非洲爪蛙芳烃基受体(从R)及其核内的转录因子(Amt),细胞色素P450(CYP)中的CYP1A6 mRNA及CYP1A7 mRNA;用免疫反应检测了CYP1A蛋白质的表达.结果表明:TCDD的染毒没有引起AhR和Arnt表达量的增加,但引起CYP1A6 mRNA及CYP1A7 mRNA表达的极显著增加,以及CYP1A蛋白质的强烈表达;TCDD强烈诱发非洲爪蛙CYP1A,且存在质量浓度依存性,使用CYP1A作为环境危险性评价具有一定的可探讨性. 相似文献
14.
Humic substances (HS) are ubiquitous natural products of decomposition of dead organic matter. HS is present in most freshwaters at concentrations ranging from 0.5 to 50 mg L−1. Organic carbon can represent 20% dry weight of sediments. Recently, the interaction of dissolved HS with the aryl hydrocarbon receptor (AhR) has been demonstrated. The AhR is a cytosolic receptor to which persistent organic pollutants (POPs) can bind and many of their toxic effects are mediated through interactions with this receptor. We describe in vitro effects (using H4IIE-luc cells) of binary mixtures of various HS with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), since in contaminated environments these compounds occur simultaneously. Six out of 12 HS samples activated AhR even at environmentally relevant concentrations (17 mg L−1), but did not reach the full AhR-activation even at excessive concentration. In simultaneous exposure of H4IIE-luc to HS (17 mg L−1) and TCDD (1.2 pM) without any preincubation prior to exposure, either significant additive or facilitative effects were observed. No negative interactions, due to possible sorption of TCDD to HS was observed. Nevertheless, if the HS–TCDD binary mixture was preincubated for 6 days prior to the exposure on H4IIE-luc cells, the additive and facilitative effects were less due to possible sorption of TCDD onto HS. Similar results were obtained from analogous experiments with greater concentrations of both TCDD and HS. 相似文献
15.
Gustavsson L Hollert H Jonsson S van Bavel B Engwall M 《Environmental science and pollution research international》2007,14(3):202-211
Goal, Scope and Background Sweden has prohibited the deposition of organic waste since January, 2005. Since 1 million tons of sludge is produced every
year in Sweden and the capacity for incineration does not fill the demands, other methods of sludge management have to be
introduced to a larger degree. One common method in the USA and parts of Europe is the use of wetlands to treat wastewater
and sewage sludge. The capacity of reed beds to affect the toxicity of a complex mixture of nitroaromatics in sludge, however,
is not fully elucidated. In this study, an industrial sludge containing explosives and pharmaceutical residues was therefore
treated in artificial reed beds and the change in toxicity was studied. Nitroaromatic compounds, which are the main ingredients
of many pharmaceuticals and explosives, are well known to cause cytotoxicity and genotoxicity. Recently performed studies
have also showed that embryos of zebrafish (Danio rerio) are sensitive to nitroaromatic compounds. Therefore, we tested the sludge passing through constructed wetlands in order
to detect any changes in levels of embryotoxicity, genotoxicity and dioxin-like activity (AhR-agonists). We also compared
unplanted and planted systems in order to examine the impact of the root system on the fate of the toxicants.
Methods An industrial sludge containing a complex mixture of nitroaromatics was added daily to small-scale constructed wetlands (vertical
flow), both unplanted and planted with Phragmites australis. Sludge with an average dry weight of 1.25%, was added with an average hydraulic loading rate of 1.2 L/day. Outgoing water
was collected daily and stored at −20°C. The artificial wetland sediment was Soxhlet extracted, followed by clean-up with
multi-layer silica, or extracted by ultrasonic treatment, yielding one organic extract and one water extract of the same sample.
Genotoxicity of the extracts was measured according to the ISO protocol for the umu-C genotoxicity assay (ISO/TC 147/SC 5/WG9
N8), using Salmonella typhimurium TA1535/pSK1002 as test organism. Embryotoxicity and teratogenicity were studied using the fish egg assay with zebrafish (Danio rerio) and the dioxin-like activity was measured using the DR-CALUX assay. Chemical analyses of nitroaromatic compounds were performed
using Solid Phase Micro Extraction (SPME) and GC-MS.
Results Organic extracts of the bed material showed toxic potential in all three toxicity tests after two years of sludge loading.
There was a difference between the planted and the unplanted beds, where the toxicity of organic extracts overall was higher
in the bed material from the planted beds. The higher toxicity of the planted beds could have been caused by the higher levels
of total carbon in the planted beds, which binds organic toxicants, and by enrichment caused by lower volumes of outgoing
water from the planted beds.
Discussion Developmental disorders were observed in zebrafish exposed directly in contact to bed material from unplanted beds, but not
in fish exposed to bed material from planted beds. Hatching rates were slightly lower in zebrafish exposed to outgoing water
from unplanted beds than in embryos exposed to outgoing water from planted beds. Genotoxicity in the outgoing water was below
detection limit for both planted and unplanted beds. Most of the added toxicants via the sludge were unaccounted for in the
outgoing water, suggesting that the beds had toxicant removal potential, although the mechanisms behind this remain unknown.
Conclusions During the experimental period, the beds received a sludge volume (dry weight) of around three times their own volume. In
spite of this, the toxicity in the bed material was lower than in the sludge. Thus, the beds were probably able to actually
decrease the toxicity of the added, sludge-associated toxicants. When testing the acetone extracts of the bed material, the
planted bed showed a higher toxicity than the unplanted beds in all three toxicity tests. The toxicity of water extracts from
the unplanted beds, detected by the fish egg assay, were higher than the water extracts from the planted beds. No genotoxicity
was detected in outgoing water from either planted or unplanted beds. All this together indicates that the planted reed beds
retained semi-lipophilic acetone-soluble toxic compounds from the sludge better than the unplanted beds, which tended to leak
out more of the water soluble toxic compounds in the outgoing water. The compounds identified by SPME/GC in the outgoing water
were not in sufficient concentrations to have caused induction in the genotoxicity test.
Recommendations and Perspectives This study has pointed out the benefits of using constructed wetlands receiving an industrial sludge containing a complex
mixture of nitroaromatics to reduce toxicity in the outgoing water. The water from planted, constructed wetlands could therefore
be directed to a recipient without further cleaning. The bed material should be investigated over a longer period of time
in order to evaluate potential accumulation and leakage prior to proper usage or storage. The plants should be investigated
in order to examine uptake and possible release when the plant biomass is degraded.
This article has been developed on the basis of a presentation given at the Annual meeting of SETAC Europe German Language
Branch 2004 in Aachen.
ESS-Submission Editor: Dr. Ludek Blaha (blaha@recetox.muni.cz) 相似文献
16.
《环境科学学报(英文版)》2023,35(3):650-661
The wide use of pesticides has seriously threatened human health and the survival of beneficial organisms. The fungicide mepanipyrim is widely used in viticulture practices. Studies of mepanipyrim-induced toxicity in organisms are still scarce, especially studies on cardiotoxicity. In this study, we aimed to investigate mepanipyrim-induced cardiotoxicity in zebrafish (Danio rerio) larvae. We found that mepanipyrim could induce cardiotoxicity by altering the heart rate and cardiomyocyte diameter of larvae. Meanwhile, RNA sequencing and RT-qPCR data indicated that mepanipyrim exposure could dramatically alter the mRNA expression of calcium signaling pathway-, cardiac muscle contraction-, and oxidative respiratory chain-related genes. Interestingly, by the CALUX cell bioassay, we found that most cytochrome c oxidase (COX) family genes exhibited potential AhR-regulated activity, suggesting that mepanipyrim induced cardiotoxicity via a novel AhR-regulated manner in larvae. Additionally, the AhR antagonist CH223191 could effectively prevent mepanipyrim-induced cardiotoxicity in zebrafish larvae. In conclusion, the AhR agonist mepanipyrim could induce cardiotoxicity in a novel unreported AhR-regulated manner, which could specifically affect the expression of COX family genes involved in the mitochondrial oxidative respiratory chain. Our data will help explain the toxic effects of mepanipyrim on organisms and provide new insight into the AhR agonistic activity pesticide-induced cardiotoxicity. 相似文献
17.
Hydroxylated polycyclic aromatic hydrocarbons (OH-PAH) with less than four rings are frequently found in the environment, whereas the toxicities associated with these compounds remain unclear. In this study, aryl hydrocarbon receptor (AhR)–ligand binding activities of OH-PAH were investigated by using a recombinant yeast assay system. The majority of the OH-PAH tested showed AhR–ligand binding activities, especially, when the hydroxylated derivatives of naphthalene were incubated with recombinant yeast. The structure–activity relationship between AhR activity and molecular weight or the octanol–water partition coefficient value of OH-PAH displayed significant correlations. These findings indicate that the site and number of hydroxy-groups substituted on PAH skeleton apparently influenced the AhR – ligand binding activity in the recombinant yeast assay. 相似文献
18.
ZHOU Hai-long ZHANG Lin-bao LIAO Chun-yang WEI Shuang-shuang ZHENG Ji-ping XUE Qin-zhao 《生态毒理学报》2010,5(1):9-17
过去30年,随着工农业的不断发展,由持久性有机污染物(POPs)导致的癌症患者不断增加.目前POPs已广泛存在于水生态系统中,对水生动物的生长发育、种群繁衍、群落结构等产生重要影响.虽然POPs对水生动物的毒理机制非常复杂,但研究表明其毒理机制主要通过芳香烃受体通道(Ah Rpathway)来进行调控.为全面理解水生动物AhR通道中每一个基因在毒理调控过程中的作用,论文从水生动物芳香烃通道的角度详细阐述了POPs的毒理机制,同时对水生动物中POPs的早期监测进行了讨论,最后提出了未来POPs毒理机制研究的发展方向. 相似文献
19.
Erika Andersson Anna Rotander Thomas von Kronhelm Anna Berggren Per Ivarsson Henner Hollert Magnus Engwall 《Environmental science and pollution research international》2009,16(5):521-530
Background, aim, and scope Degradation of the 16 US EPA priority PAHs in soil subjected to bioremediation is often achieved. However, the PAH loss is
not always followed by a reduction in soil toxicity. For instance, bioanalytical testing of such soil using the chemical-activated
luciferase gene expression (CALUX) assay, measuring the combined effect of all Ah receptor (AhR) activating compounds, occasionally
indicates that the loss of PAHs does not correlate with the loss of Ah receptor-active compounds in the soil. In addition,
standard PAH analysis does not address the issue of total toxicant bioavailability in bioremediated soil.
Materials and methods To address these questions, we have used the CALUX AhR agonist bioassay and the Comet genotoxicity bioassay with RTL-W1 cells
to evaluate the toxic potential of different extracts from a PAH-contaminated soil undergoing large-scale bioremediation.
The extracts were also chemically analyzed for PAH16 and PCDD/PCDF. Soil sampled on five occasions between day 0 and day 274
of biological treatment was shaken with n-butanol with vortex mixing at room temperature to determine the bioavailable fraction
of contaminants. To establish total concentrations, parts of the same samples were extracted using an accelerated solvent
extractor (ASE) with toluene at 100°C. The extracts were tested as inducers of AhR-dependent luciferase activity in the CALUX
assay and for DNA breakage potential in the Comet bioassay.
Results The chemical analysis of the toluene extracts indicated slow degradation rates and the CALUX assay indicated high levels of
AhR agonists in the same extracts. Compared to day 0, the bioavailable fractions showed no decrease in AhR agonist activity
during the treatment but rather an up-going trend, which was supported by increasing levels of PAHs and an increased effect
in the Comet bioassay after 274 days. The bio-TEQs calculated using the CALUX assay were higher than the TEQs calculated from
chemical analysis in both extracts, indicating that there are additional toxic PAHs in both extracts that are not included
in the chemically derived TEQ.
Discussion The response in the CALUX and the Comet bioassays as well as the chemical analysis indicate that the soil might be more toxic
to organisms living in soil after 274 days of treatment than in the untreated soil, due to the release of previously sorbed
PAHs and possibly also metabolic formation of novel toxicants.
Conclusions Our results put focus on the issue of slow degradation rates and bioavailability of PAHs during large-scale bioremediation
treatments. The release of sorbed PAHs at the investigated PAH-contaminated site seemed to be faster than the degradation
rate, which demonstrates the importance of considering the bioavailable fraction of contaminants during a bioremediation process.
Recommendations and perspectives It has to be ensured that soft remediation methods like biodegradation or the natural remediation approach do not result in
the mobilization of toxic compounds including more mobile degradation products. For PAH-contaminated sites this cannot be
assured merely by monitoring the 16 target PAHs. The combined use of a battery of biotests for different types of PAH effects
such as the CALUX and the Comet assay together with bioavailability extraction methods may be a useful screening tool of bioremediation
processes of PAH-contaminated soil and contribute to a more accurate risk assessment. If the bioremediation causes a release
of bound PAHs that are left undegraded in an easily extracted fraction, the soil may be more toxic to organisms living in
the soil as a result of the treatment. A prolonged treatment time may be one way to reduce the risk of remaining mobile PAHs.
In critical cases, the remediation concept might have to be changed to ex situ remediation methods. 相似文献
20.
2,3,7,8-Tetrachlorodibenzo(p)dioxin (TCDD) has been known to induce inflammatory signaling in a number of cell types and tissues. We found that in U937 macrophages TCDD causes rapid activation of cytosolic phospholipase A2 (cPLA2) within 30 min as judged by the increase in the serine 505 phosphorylated form of cPLA2 protein and the increased cellular release of free arachidonic acid. This initial action of TCDD is accompanied with the up-regulation of an important inflammation marker, COX-2 mRNA expression within 1 h, and by 3 h, several other markers become up-regulated. These effects appear to be dependent on the initial increase in the intracellular concentration of Ca2+, and activation of cPLA2 and COX-2. A comparative study among three different human cell lines showed that activation of COX-2 within 1 h of action of TCDD is a common feature exhibited by all cell lines. On the other hand, the U937 macrophage line appears to be unique among them with respect to its ability to activate TNF-α and IL-8 mRNA expressions, and not requiring Src kinase in propagating the initial signaling of cPLA2. Based on the rapidity of activation of cPLA2 and COX-2, which occurs within 1 h of cell exposure to TCDD, when no change in mRNA expression of CYP1A1 has been observed, it is apparent that this unique action of TCDD is carried out through a distinct “nongenomic” pathway which, is clearly discernable from the classical, “genomic” action pathway of the AhR by not requiring the participation of ARNT. 相似文献