Publications by authors named "Pei-Hsin Chou"

24 Publications

  • Page 1 of 1

Revisiting of persistent organic pollution occurrence and distribution in the surface sediment along western Taiwan coast.

Mar Pollut Bull 2021 Dec 8;173(Pt B):113118. Epub 2021 Nov 8.

National Museum of Marine Biology and Aquarium, Pingtung, Taiwan; Institute of Marine Biology, National Dong Hwa University, Pingtung, Taiwan. Electronic address:

Levels of persistent organic pollutants (POPs), including PAHs, PCBs, DDTs, and PBDEs, were measured in sediment collected from along the Taiwan coast and compared to previous studies. The dominant POPs were PAHs, followed by PCBs, PBDEs, and DDTs. The highest levels of PAHs and PCBs were found in sediment from harbors in southern Taiwan, which are surrounded by densely populated areas and affected by multiple industrial activities. In contrast, significantly higher levels of PBDEs were found at the northern coastline, which has a higher population and includes the metropolitan Taipei area. Using diagnostic PAH ratios, the predominant sources of PAHs in coastal Taiwan was determined to be pyrolytic-related activities. The main component of each POP was low- to moderately-chlorinated congeners, p,p'-DDE and BDE209, respectively. Further studies are required to assess the impact of these POPs on marine and coastal ecosystem.
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http://dx.doi.org/10.1016/j.marpolbul.2021.113118DOI Listing
December 2021

Occurrence of class 1 integrons carrying two copies of the bla gene in carbapenem-non-susceptible Citrobacter freundii and Raoultella ornithinolytica isolated from wastewater.

J Glob Antimicrob Resist 2021 09 14;26:230-232. Epub 2021 Jul 14.

Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

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http://dx.doi.org/10.1016/j.jgar.2021.06.014DOI Listing
September 2021

Algal extracellular organic matter mediated photocatalytic degradation of estrogens.

Ecotoxicol Environ Saf 2021 Feb 23;209:111818. Epub 2020 Dec 23.

Graduate Institute of Environmental Engineering, National Taiwan University, Taipei 10617, Taiwan; Water Innovation, Low Carbon and Environmental Sustainability Research Center, National Taiwan University, Taipei, 106, Taiwan. Electronic address:

Estrogens are among the most concerned emerging contaminants in the wastewater treatment effluent due to their sexual disruption in aquatic wildlife. The use of microalgae for secondary wastewater effluent polishing is a promising approach due to the economic benefit and value-added products. In this study, three microalgae species, including Selenastrum capricornutum, Scenedesmus quadricauda and Chlorella vulgaris were selected to conduct batch experiments to examine important mechanisms, especially the role of algal extracellular organic matter (AEOM) on two selected estrogens (17β-estradiol, E2 and 17α-ethynylestradiol, EE2) removal. Results showed that estrogens could not be significantly degraded under visible light irradiation and adsorption of estrogens by microalgae was negligible. All three living microalgae cultures have ability to remove E2 and EE2, and Selenastrum capricornutum showed the highest E2 and EE2 removal efficiency of 91% and 83%, respectively, corresponding to the reduction of predicted estrogenic activity of 86%. AEOM from three microalgae cultures could induce photodegradation of estrogens, and AEOM from Selenastrum capricornutum and Chlorella vulgaris achieved 100% of E2 and EE2 removal under visible light irradiation. Fluorescence excitation-emission matrix spectroscopy identified humic/fulvic-like substances in AEOM from three microalgae cultures, which might be responsible for inducing the indirect photolysis of E2 and EE2. Therefore, in the living microalgae cultures, the major estrogens removal mechanisms should include biotransformation as well as AEOM meditated photocatalytic degradation. Since removal rates through photodegradation could be faster than biotransformation, the AEOM mediated photocatalytic degradation can play a potential role to remove emerging contaminants when using microalgae technology for wastewater effluent treatment.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111818DOI Listing
February 2021

In vitro and in vivo screening for environmentally friendly benzophenone-type UV filters with beneficial tyrosinase inhibition activity.

Water Res 2020 Oct 20;185:116208. Epub 2020 Jul 20.

Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan. Electronic address:

Benzophenones (BPs) are a group of chemically similar organic compounds commonly used in formulations of sunscreen and other personal care products as UV filters to protect our skin against sunlight overexposure. Studies have shown that the occurrence of certain BPs (e.g., BP-3 and its metabolite BP-1) in multiple environmental matrices may increase the incidence of coral planulae bleaching and estrogenic effects on aquatic life. Currently, most BPs are not yet comprehensively screened in vitro and in vivo for their ecotoxicity under environmentally relevant concentrations. This study systematically assessed the in vitro and in vivo toxicity and activity of the 7 most commonly used BPs (BP-1, BP-2, BP-3, BP-4, BP-6, BP-7 and BP-8) to select BP alternatives with lower ecotoxicity and extra beneficial functions. BP-2 (LC = 18.43 µM) was least toxic and BP-3 (LC = 4.10 µM) and BP-8 (LC =1.62 µM) were less and most toxic, respectively, in terms of 96-hr acute mortality of medaka larvae. BP-2 at environmentally relevant concentrations (5-50 nM) did not significantly alter locomotion and oxidative stress responses of medaka larvae from 24-hr to 7-day exposure, whereas BP-3 and BP-8 at 5 nM induced hypoactivity or changed fish swimming angles. Only BP-2 was able to inhibit in vitro mushroom tyrosinase activity, with EC value 19.7 µM. Also, BP-2 could effectively suppress melanin formation and tyrosinase activity in zebrafish embryos. Among the 7 tested BPs, BP-2 was the least toxic and the most environmentally friendly UV filter with extra benefit for tyrosinase inhibition and could be a promising alternative to the use of toxic BPs.
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http://dx.doi.org/10.1016/j.watres.2020.116208DOI Listing
October 2020

Assessing the endocrine disrupting potentials and genotoxicity in environmental samples from Taiwanese rivers.

Genes Environ 2019 30;41:24. Epub 2019 Dec 30.

1Department of Environmental Engineering, National Cheng Kung University, 1, University Road, Tainan, 701 Taiwan.

Background: Surface waters receive a variety of organic pollutants via wastewater discharge, and sediment represents a sink for hydrophobic contaminants. In this study, we used in vitro yeast-based reporter gene assays and a Rec-assay to examine the occurrence of endocrine disrupting activities and genotoxic potentials in samples collected from three Taiwanese rivers. Levels of 51 polycyclic aromatic hydrocarbons (PAHs) in muscles of fish captured from same rivers were also analyzed to assess in vivo pollution of PAHs.

Results: Antagonist activities for androgen receptor and retinoid X receptor (RXR) were detected in river water extracts at environmentally relevant concentrations., and sediment extracts exhibited RXR agonist, RXR antagonist, and genotoxic potentials concurrently. Σ16 PAHs in fish muscles ranged from 44.9-242.4 ng g dry weight, representing 38 to 59% of the total 51 PAHs concentrations, and methylated PAHs of low molecular weight PAHs were often detected as well.

Conclusion: Taiwanese river sediment samples concomitantly exhibited RXR disrupting potentials and genotoxic activities, whereas RXR agonist and antagonist activities were simultaneously detected in several dry-season sediment extracts. PAH levels in fish muscles were categorized as minimally polluted by aromatic compounds, nonetheless, the presence of methylated PAHs in muscles samples may be of concern owing to the higher toxic potentials than their parent compounds.
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http://dx.doi.org/10.1186/s41021-019-0140-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937667PMC
December 2019

Biodegradation of the endocrine disrupter 4-t-octylphenol by the non-ligninolytic fungus Fusarium falciforme RRK20: Process optimization, estrogenicity assessment, metabolite identification and proposed pathways.

Chemosphere 2020 Feb 14;240:124876. Epub 2019 Sep 14.

Institute of Environmental Engineering, National Central University, Taoyuan 32001, Taiwan. Electronic address:

4-t-octylphenol (4-t-OP), a well-known endocrine disrupting compound, is frequently found in various environmental compartments at levels that may cause adverse effects to the ecosystem and public health. To date, most of the studies that investigate microbial transformations of 4-t-OP have focused on the process mediated by bacteria, ligninolytic fungi, or microbial consortia. There is no report on the complete degradation mechanism of 4-t-OP by non-ligninolytic fungi. In this study, we conducted laboratory experiments to explore and characterize the non-ligninolytic fungal strain Fusarium falciforme RRK20 to degrade 4-t-OP. Using the response surface methodology, the initial biomass concentration and temperature were the factors identified to be more influential on the efficiency of the biodegradation process as compared with pH. Under the optimized conditions (i.e., 28 °C, pH 6.5 with an initial inoculum density of 0.6 g L), 25 mg L 4-t-OP served as sole carbon source was completely depleted within a 14-d incubation; addition of low dosage of glucose was shown to significantly accelerate 4-t-OP degradation. The yeast estrogenic screening assay further confirmed the loss of estrogenic activity during the biodegradation process, though a longer incubation period was required for complete removal of estrogenicity. Metabolites identified by LC-MS/MS revealed that strain RRK20 might degrade 4-t-OP as sole energy source via alkyl chain oxidation and aromatic ring hydroxylation pathways. Together, these results not only suggest the potential use of non-ligninolytic fungi like strain RRK20 in remediation of 4-t-OP contaminated environments but may also improve our understanding of the environmental fate of 4-t-OP.
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http://dx.doi.org/10.1016/j.chemosphere.2019.124876DOI Listing
February 2020

Characteristics of Carbapenemase-Producing Enterobacteriaceae in Wastewater Revealed by Genomic Analysis.

Antimicrob Agents Chemother 2018 05 26;62(5). Epub 2018 Apr 26.

Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Wastewater is considered a major source of antibiotic-resistant bacteria released into the environment. Here, we characterized carbapenemase-producing (CPE) in wastewater by whole-genome analysis. Wastewater samples ( = 40) were collected from municipal wastewater treatment plants and hospital wastewater in Japan and Taiwan. Samples were screened for CPE using selective media, and the obtained isolates were sequenced using an Illumina MiSeq. The isolates ( = 45) included the following microorganisms: ( = 12), ( = 10), complex ( = 10), ( = 8), ( = 2), ( = 1), ( = 1), and ( = 1). Among the 45 isolates, 38 harbored at least one carbapenemase-encoding gene. Of these, the (, , and ) genes were found in 29 isolates. The genes were situated in novel class 1 integrons, but the integron structures were different between the Japanese (In1439 with and In1440 with ) and Taiwanese (In1441 with and In1442 with ) isolates. Other carbapenemase-encoding genes (, , , , and ) were found in one to three isolates. Notably, class 1 integrons previously reported among clinical isolates obtained in the same regions as the present study, namely, In477 with and In73 with , were found among the Japanese and Taiwanese isolates, respectively. The results indicate that CPE with various carbapenemase-encoding genes in different genetic contexts were present in biologically treated wastewater, highlighting the need to monitor for antibiotic resistance in wastewater.
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http://dx.doi.org/10.1128/AAC.02501-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923170PMC
May 2018

7-ketocholesterol and 27-hydroxycholesterol decreased doxorubicin sensitivity in breast cancer cells: estrogenic activity and mTOR pathway.

Oncotarget 2017 Sep 2;8(39):66033-66050. Epub 2017 Aug 2.

National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan, R.O.C.

Hypercholesterolemia is one of the risk factors for poor outcome in breast cancer therapy. To elucidate the influence of the main circulating oxysterols, cholesterol oxidation products, on the cell-killing effect of doxorubicin, cells were exposed to oxysterols at a subtoxic concentration. When cells were exposed to oxysterols in fetal bovine serum-supplemented medium, 7-ketocholesterol (7-KC), but not 27-hydroxycholesterol (27-HC), decreased the cytotoxicity of doxorubicin in MCF-7 (high estrogen receptor (ER)α/ERβ ratio) cells and the decreased cytotoxicity was restored by the P-glycoprotein inhibitor verapamil. 7-KC stimulated the efflux function of P-glycoprotein and reduced intracellular doxorubicin accumulation in MCF-7 but not in ERα(-) MDA-MB-231 and the resistant MCF-7/ADR cells. In MCF-7 cells, 7-KC increased the mRNA and protein levels of P-glycoprotein. The 7-KC-suppressed doxorubicin accumulation was restored by the fluvestrant and ERα knockdown. In a yeast reporter assay, the ERα activation by 7-KC was more potent than 27-HC. 7-KC, but not 27-HC, stimulated the expression of an ER target, Trefoil factor 1 in MCF-7 cells. When charcoal-stripped fetal bovine serum was used, both 7-KC and 27-HC induced Trefoil factor 1 expression and reduced doxorubicin accumulation in MCF-7 cells. 7-KC-reduced doxorubicin accumulation could be reversed by inhibitors of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin (mTOR). These findings demonstrate that 7-KC decreases the cytotoxicity of doxorubicin through the up-regulation of P-glycoprotein in an ERα- and mTOR-dependent pathway. The 7-KC- and 27-HC-elicited estrogenic effects are crucial in the P-glycoprotein induction in breast cancer cells.
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http://dx.doi.org/10.18632/oncotarget.19789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630390PMC
September 2017

Detection of endocrine active substances in the aquatic environment in southern Taiwan using bioassays and LC-MS/MS.

Chemosphere 2016 Jun 10;152:214-20. Epub 2016 Mar 10.

Department of Environmental Engineering, National Cheng Kung University, No. 1, University Road, Tainan, 70101, Taiwan, ROC. Electronic address:

Endocrine active substances, including naturally occurring hormones and various synthetic chemicals have received much concern owing to their endocrine disrupting potencies. It is essential to monitor their environmental occurrence since these compounds may pose potential threats to biota and human health. In this study, yeast-based reporter assays were carried out to investigate the presence of (anti-)androgenic, (anti-)estrogenic, and (anti-)thyroid compounds in the aquatic environment in southern Taiwan. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was also used to measure the environmental concentrations of selected endocrine active substances for assessing potential ecological risks and characterizing contributions to the endocrine disrupting activities. Bioassay results showed that anti-androgenic (ND-7489 μg L(-1) flutamide equivalent), estrogenic (ND-347 ng L(-1) 17β-estradiol equivalent), and anti-thyroid activities were detected in the dissolved and particulate phases of river water samples, while anti-estrogenic activities (ND-10 μg L(-1) 4-hydroxytamoxifen equivalent) were less often found. LC-MS/MS analysis revealed that anti-androgenic and estrogenic contaminants, such as bisphenol A, triclosan, and estrone were frequently detected in Taiwanese rivers. In addition, their risk quotient values were often higher than 1, suggesting that they may pose an ecological risk to the aquatic biota. Further identification of unknown anti-androgenic and estrogenic contaminants in Taiwanese rivers may be necessary to protect Taiwan's aquatic environment.
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http://dx.doi.org/10.1016/j.chemosphere.2016.02.115DOI Listing
June 2016

Application of a multiwalled carbon nanotube-chitosan composite as an electrode in the electrosorption process for water purification.

Chemosphere 2016 Mar 20;146:113-20. Epub 2015 Dec 20.

Graduate Institute of Environmental Engineering, National Taiwan University, Taipei, 10617, Taiwan. Electronic address:

In this study, a multiwalled carbon nanotubes-chitosan (CNTs-CS) composite electrode was fabricated to enable water purification by electrosorption. The CNTs-CS composite electrode was shown to possess excellent capacitive behaviors and good pore accessibility by electrochemical impedance spectroscopy, galvanostatic charge-discharge, and cyclic voltammetry measurements in 1 M H2SO4 electrolyte. Moreover, the CNTs-CS composite electrode showed promising performance for capacitive water desalination. At an electric potential of 1.2 V, the electrosorption capacity and electrosorption rate of NaCl ions on the CNTs-CS composite electrode were determined to be 10.7 mg g(-1) and 0.051 min(-1), respectively, which were considerably higher than those of conventional activated electrodes. The improved electrosorption performance could be ascribed to the existence of mesopores. Additionally, the feasibility of electrosorptive removal of aniline from an aqueous solution has been demonstrated. Upon polarization at 0.6 V, the CNTs-CS composite electrode had a larger electrosorption capacity of 26.4 mg g(-1) and a higher electrosorption rate of 0.006 min(-1) for aniline compared with the open circuit condition. The enhanced adsorption resulted from the improved affinity between aniline and the electrode under electrochemical assistance involving a nonfaradic process. Consequently, the CNT-CS composite electrode, exhibiting typical double-layer capacitor behavior and a sufficient potential range, can be a potential electrode material for application in the electrosorption process.
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http://dx.doi.org/10.1016/j.chemosphere.2015.12.012DOI Listing
March 2016

Exploring potential contributors to endocrine disrupting activities in Taiwan's surface waters using yeast assays and chemical analysis.

Chemosphere 2015 Nov 24;138:814-20. Epub 2015 Aug 24.

Department of Environmental Engineering, National Cheng Kung University, No. 1, University Road, Tainan 70101, Taiwan.

Surface waters serve as sinks for anthropogenic contaminants, including naturally occurring hormones and a variety of synthetic endocrine active substances. To investigate the presence of endocrine active contaminants in the aquatic environment in Taiwan, river water and suspended solids were analyzed by yeast assays to examine the distribution of estrogenic, androgenic, and aryl hydrocarbon receptor agonist activities. The results showed that dry-season river samples exhibited strong estrogenic and aryl hydrocarbon receptor agonist activities, but no androgenic activity was detected. Owing to the ubiquitous detection of estrogenic activities in Taiwan's surface waters, samples were further subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for quantification of selected estrogenic compounds. LC-MS/MS results indicated that natural estrogens, such as estrone and 17β-estradiol were often the most contributing compounds for the bioassay-derived estrogenic activities due to their strong estrogenic potencies and high detection frequencies, whereas high concentrations of bisphenol A and nonylphenol also posed a threat to the aquatic ecosystems in Taiwan. Water samples eliciting strong estrogenic activities were further fractionated using high performance liquid chromatography, and significant estrogenic activities were detected in fractions containing estrone, 17β-estradiol, 17α-ethynylestradiol, and bisphenol A. Also, the presence of unidentified estrogenic compounds was found in few river water samples. Further identification of unknown endocrine active substances is necessary to better protect the aquatic environment in Taiwan.
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http://dx.doi.org/10.1016/j.chemosphere.2015.08.016DOI Listing
November 2015

Azole-resistant Aspergillus fumigatus isolates carrying TR₃₄/L98H mutations in Taiwan.

Mycoses 2015 Sep 27;58(9):544-9. Epub 2015 Jul 27.

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.

Cumulative evidence described the emergence and geographical expansion of azole-resistant A. fumigatus associated with azole treatment failure. To investigate the status of azole resistance in A. fumigatus in Taiwan, we studied 38 A. fumigatus clinical isolates cultivated from 31 patients at two teaching hospitals from 2011 to 2014. Three isolates obtained from respiratory samples of two azole-naïve patients with pulmonary aspergillosis were found to display multi-azole resistance and cross resistance to agricultural azole fungicides, and all carried TR34/L98H mutations in cyp51A gene. The prevalence rates of azole resistance were 7.9% and 6.5% based on isolates and patients respectively. A phylogenetic analysis suggested genetic diversity of the TR34/L98H isolates in Taiwan, including a unique genotype distinct from strains outside Taiwan. The result underlines the emergence of such isolates in Taiwan as well, emphasising the importance of further surveillance for azole-resistant A. fumigatus and implementation of strategies that prevent fungicide-driven resistance selection.
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http://dx.doi.org/10.1111/myc.12354DOI Listing
September 2015

Clinical implications of species identification in monomicrobial Aeromonas bacteremia.

PLoS One 2015 13;10(2):e0117821. Epub 2015 Feb 13.

Departments of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Departments of Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan.

Background: Advances in Aeromonas taxonomy have led to the reclassification of aeromonads. Hereon, we aimed to re-evaluate the characteristics of Aeromonas bacteremia, including those of a novel species, Aeromonas dhakensis.

Methodology/principal Findings: A retrospective study of monomicrobial Aeromonas bacteremia at a medical center in southern Taiwan from 2004-2011 was conducted. Species identification was based on rpoB sequencing. Of bacteremia of 153 eligible patients, A. veronii (50 isolates, 32.7%), A. dhakensis (48, 31.4%), A. caviae (43, 28.1%), and A. hydrophila (10, 6.5%) were the principal causative species. A. dhakensis and A. veronii bacteremia were mainly community-acquired and presented as primary bacteremia, spontaneous bacterial peritonitis, or skin and soft-tissue infection, whereas A. caviae was associated with hospital-onset bacteremia. The distribution of the AmpC β-lactamase and metallo-β-lactamase genes was species-specific: bla(AQU-1), bla(MOX), or bla(CepH) was present in A. dhakensis, A. caviae, or A. hydrophila, respectively, and bla(CphA) was present in A. veronii, A. dhakensis, and A. hydrophila. The cefotaxime resistance rates of the A. caviae, A. dhakensis, and A. hydrophila isolates were higher than that of A. veronii (39.5%%, 25.0%, and 30% vs. 2%, respectively). A. dhakensis bacteremia was linked to the highest 14-day sepsis-related mortality rate, followed by A. hydrophila, A. veronii, and A. caviae bacteremia (25.5%, 22.2%, 14.0%, and 4.7%, respectively; P = 0.048). Multivariate analysis revealed that A. dhakensis bacteremia, active malignancies, and a Pitt bacteremia score ≥ 4 was an independent mortality risk factor.

Conclusions/significance: Characteristics of Aeromonas bacteremia vary between species. A. dhakensis prevalence and its associated poor outcomes suggest it an important human pathogen.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117821PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334500PMC
November 2015

Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish.

J Hazard Mater 2014 Jul 6;277:150-8. Epub 2014 Jun 6.

Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan. Electronic address:

Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish populations in the aquatic environment.
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http://dx.doi.org/10.1016/j.jhazmat.2014.05.083DOI Listing
July 2014

Monitoring of xenobiotic ligands for human estrogen receptor and aryl hydrocarbon receptor in industrial wastewater effluents.

J Hazard Mater 2014 Jul 13;277:13-9. Epub 2014 Mar 13.

Department of Environmental Engineering, National Cheng Kung University, Tainan 70101, Taiwan; Sustainable Environment Research Laboratories, National Cheng Kung University, Tainan 70101, Taiwan.

Industrial wastewater contains a variety of toxic substances, which may severely contaminate the aquatic environment if discharged without adequate treatment. In this study, effluents from a thin film transistor liquid crystal display wastewater treatment plant and the receiving water were analyzed by bioassays and liquid chromatography-tandem mass spectrometry to investigate the presence of estrogenic compounds, aryl hydrocarbon receptor (AhR) agonists, and genotoxicants. Xenobiotic AhR agonists were frequently detected and, in particular, strong AhR agonist activity and genotoxicity were found in the suspended solids of the aeration tank outflow. The high AhR agonist activity in the final effluent (FE) and the downstream river water suggested that the treatment plant failed to remove the wastewater-related AhR agonists. In contrast, although significant estrogenic potency could be detected in raw wastewater or effluents from different treatment processes, the FE and the receiving river water exhibited no or weak estrogenicity. Instrumental analysis showed that bisphenol A was often detected in water samples. However, the investigated estrogenic compounds could only account for a small portion of the estrogenicity in the collected samples. Therefore, further investigation is necessary to identify the major estrogenic compounds and AhR agonist contaminants in the wastewater effluents.
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http://dx.doi.org/10.1016/j.jhazmat.2014.02.049DOI Listing
July 2014

Occurrence of xenobiotic ligands for retinoid X receptors and thyroid hormone receptors in the aquatic environment of Taiwan.

Mar Pollut Bull 2014 Aug 24;85(2):613-8. Epub 2014 Jan 24.

Graduate School of Science and Radiation Research Center, Osaka Prefecture University, 1-2 Gakuen-cho, Sakai, Osaka 599-8570, Japan.

Various synthetic compounds are frequently discharged into the environment via human activities. Among them, certain contaminants may disrupt normal physiological functions of wildlife and humans via interactions with nuclear receptors. To protect human health and the environment, it is important to detect environmental ligands for human nuclear receptors. In this study, yeast-based reporter gene assays were used to investigate the occurrence of xenobiotic ligands for retinoid X receptors (RXR) and thyroid hormone receptors (TR) in the aquatic environment of Taiwan. Experimental results revealed that RXR agonist/antagonist activity was detected in river water and sediment samples. In particular, high RXR agonist/antagonist activity was found in the samples collected near river mouths. Additionally, few samples also elicited significant TR antagonist activity. Our findings show that the aquatic environment of Taiwan was contaminated with RXR and TR ligands. Further study is necessary to identify these xenobiotic RXR and TR agonists and antagonists.
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http://dx.doi.org/10.1016/j.marpolbul.2014.01.025DOI Listing
August 2014

Occurrence of aryl hydrocarbon receptor agonists and genotoxic compounds in the river systems in Southern Taiwan.

Chemosphere 2014 Jul 8;107:257-264. Epub 2014 Jan 8.

Department of Environmental Engineering, National Cheng Kung University, Tainan, Taiwan.

Water and sediment samples from river systems located in Southern Taiwan were investigated for the presence of aryl hydrocarbon receptor (AhR) agonists and genotoxicants by a combination of recombinant cell assays and gas chromatography-mass spectrometry analysis. AhR agonist activity and genotoxic response were frequently detected in samples collected during different seasons. In particular, dry-season water and sediment samples from Erren River showed strong AhR agonist activity (201-1423 ng L(-1) and 1374-5631 ng g(-1) β-naphthoflavone equivalents) and high genotoxic potential. Although no significant correlation was found between AhR agonist activity and genotoxicity, potential genotoxicants in sample extracts were suggested to be causative agents for yeast growth inhibition in the AhR-responsive reporter gene assay. After high performance liquid chromatography fractionation, AhR agonist candidates were detected in several fractions of Erren River water and sediment extracts, while possible genotoxicants were only found in water extracts. In addition, polycyclic aromatic hydrocarbons, the typical contaminants showing high AhR binding affinity, were only minor contributors to the AhR agonist activity detected in Erren River sediment extracts. Our findings displayed the usefulness of bioassays in evaluating the extent of environmental contamination, which may be helpful in reducing the chances of false-negative results obtained from chemical analysis of conventional contaminants. Further research will be undertaken to identify major candidates for xenobiotic AhR agonists and genotoxicants to better protect the aquatic environments in Taiwan.
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http://dx.doi.org/10.1016/j.chemosphere.2013.12.052DOI Listing
July 2014

AQU-1, a chromosomal class C β-lactamase, among clinical Aeromonas dhakensis isolates: distribution and clinical significance.

Int J Antimicrob Agents 2013 Nov 7;42(5):456-61. Epub 2013 Sep 7.

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan.

Aeromonas dhakensis, a recently described Aeromonas sp. formerly called Aeromonas aquariorum, is associated with human infections. In this study, a chromosomal gene, blaAQU-1, was identified in A. dhakensis AAK1 that constitutes a 1143-bp open reading frame and is 87% identical to the gene encoding CepH in Aeromonas hydrophila. An Escherichia coli TOP10 cell transformant harbouring blaAQU-1 was resistant to cefotaxime but not to cefepime. mRNA expression of blaAQU-1 in the cefotaxime-resistant mutant strain AAK1m was 70-fold higher than in the wild strain AAK1. In all 16 A. dhakensis isolates (the major species of 51 consecutive Aeromonas blood isolates collected from June 1999 to June 2001) as well as in A. aquariorum MDC47(T) and A. hydrophila subsp. dhakensis LMG 19562(T), but not in the reference strains or clinical isolates of other A. hydrophila subspecies, Aeromonas caviae, Aeromonas veronii or Aeromonas enteropelogenes, blaAQU-1-related genes were detected by PCR. Overall, 13 (81%) of the 16 A. dhakensis blood isolates exhibited either cefotaxime resistance or the in vitro emergence of derepressed cefotaxime-resistant mutants. In vivo selection of an A. dhakensis resistant mutant was noted in a burn patient undergoing cefotaxime monotherapy. These observations suggest that AQU-1 is a chromosomal cephalosporinase in A. dhakensis. Cefotaxime monotherapy for severe A. dhakensis infections should be used cautiously.
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http://dx.doi.org/10.1016/j.ijantimicag.2013.08.002DOI Listing
November 2013

Transformation of bisphenol A and alkylphenols by ammonia-oxidizing bacteria through nitration.

Environ Sci Technol 2012 Apr 3;46(8):4442-8. Epub 2012 Apr 3.

Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.

Transformation of bisphenol A (BPA) by ammonia-oxidizing bacteria (AOB) Nitrosomonas europaea ATCC 19718 was investigated. On the basis of the ultraperformance liquid chromatography (UPLC) coupled to quadrupole time-of-flight mass spectrometry (Q-TOF MS) and nuclear magnetic resonance analysis, we found N. europaea could transform BPA into nitro- and dinitro-BPA, suggesting that abiotic nitration between the biogenic nitrite and BPA played a major role in the transformation of BPA in the batch AOB system. Nitrite concentrations, temperature, and pH values were the major factors to influence the reaction rate. Furthermore, the yeast estrogenic screening assay showed that the formed nitro- and dinitro-BPA had much less estrogenic activity as compared with its parent compound BPA. Similar reactions of abiotic nitration were considered for 4-n-nonylphenol (nNP) and 4-n-octylphenol (nOP) since nitro-nNP and nitro-nOP were detected by UPLC-Q-TOF MS. In addition, results from the local wastewater treatment plant (WWTP) showed the occurrence of nitro-BPA and dinitro-BPA during the biological treatment process and in the effluent, indicating that nitration of BPA is also a pathway for removal of BPA. Results of this study provided implication that AOB in the WWTPs might contribute to removal of selected endocrine-disrupting compounds (EDCs) through abiotic nitritation.
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http://dx.doi.org/10.1021/es204424tDOI Listing
April 2012

Genetic susceptibility to lung cancer.

Front Biosci (Schol Ed) 2011 Jun 1;3:1463-77. Epub 2011 Jun 1.

Department of Pathology, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Shizuoka, Japan.

Lung cancer is a highly environmental disease, but cancer researchers have long been interested in investigating genetic susceptibility to lung cancer. This paper is a historical review and provides updated perspectives on lung cancer susceptibility research. The recent introduction of easier genotyping methods and the availability of an almost complete human genome database facilitated the association study to thousands of cases and controls for millions of genetic markers. Discoveries in the field of behavior genetics, that is, the genetic aspects of smoking behavior and nicotine addiction, unexpectedly indicated that polymorphisms in the human central nervous system play an important role in eventually leading to lung cancer. These findings were achieved by using comprehensive approaches, such as a genome, transcriptome, or proteome approach, and the studies were often conducted without a hypothesis. Another-omics approach, the "adductome" or "exposome" approach to how life style information can be integrated into the framework of genetic association studies, has recently emerged. These new paradigms will influence the area of lung cancer risk evaluation in genome cohort studies.
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http://dx.doi.org/10.2741/237DOI Listing
June 2011

Detection of lipid peroxidation-induced DNA adducts caused by 4-oxo-2(E)-nonenal and 4-oxo-2(E)-hexenal in human autopsy tissues.

Chem Res Toxicol 2010 Sep;23(9):1442-8

Research Center for Environmental Quality Management, Kyoto University, Otsu, Shiga, 520-0811, Japan.

DNA adducts are produced both exogenously and endogenously via exposure to various DNA-damaging agents. Two lipid peroxidation (LPO) products, 4-oxo-2(E)-nonenal (4-ONE) and 4-oxo-2(E)-hexenal (4-OHE), induce substituted etheno-DNA adducts in cells and chemically treated animals, but the adduct levels in humans have never been reported. It is important to investigate the occurrence of 4-ONE- and 4-OHE-derived DNA adducts in humans to further understand their potential impact on human health. In this study, we conducted DNA adductome analysis of several human specimens of pulmonary DNA as well as various LPO-induced DNA adducts in 68 human autopsy tissues, including colon, heart, kidney, liver, lung, pancreas, small intestine, and spleen, by liquid chromatography tandem mass spectrometry. In the adductome analysis, DNA adducts derived from 4-ONE and 4-OHE, namely, heptanone-etheno-2'-deoxycytidine (HεdC), heptanone-etheno-2'-deoxyadenosine (HεdA), and butanone-etheno-2'-deoxycytidine (BεdC), were identified as major adducts in one human pulmonary DNA. Quantitative analysis revealed 4-ONE-derived HεdC, HεdA, and heptanone-etheno-2'-deoxyguanosine (HεdG) to be ubiquitous in various human tissues at median values of 10, 15, and 8.6 adducts per 10(8) bases, respectively. More importantly, an extremely high level (more than 100 per 10(8) bases) of these DNA adducts was observed in several cases. The level of 4-OHE-derived BεdC was highly correlated with that of HεdC (R(2) = 0.94), although BεdC was present at about a 7-fold lower concentration than HεdC. These results suggest that 4-ONE- and 4-OHE-derived DNA adducts are likely to be significant DNA adducts in human tissues, with potential for deleterious effects on human health.
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http://dx.doi.org/10.1021/tx100047dDOI Listing
September 2010

DNA modifications by the omega-3 lipid peroxidation-derived mutagen 4-oxo-2-hexenal in vitro and their analysis in mouse and human DNA.

Chem Res Toxicol 2010 Mar;23(3):630-6

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

4-Oxo-2-hexenal (4-OHE), which forms a 2'-deoxyguanosine (dG) adduct in a model lipid peroxidation system, is mutagenic in the Ames test. It is generated by the oxidation of omega-3 fatty acids and is commonly found in dietary fats, such as fish oil, perilla oil, rapeseed oil, and soybean oil. 4-OHE also forms adducts with 2'-deoxyadenosine (dA), 2'-deoxycytidine (dC), and 5-methyl-2'-deoxycytidine (5-Me-dC) in DNA. In this study, we characterized the structures of these adducts in detail. We measured the amounts of 4-OHE-DNA adducts in mouse organs by LC/MS/MS, after 4-OHE was orally administered to mice. The 4-OHE-dA, 4-OHE-dC, 4-OHE-dG, and 4-OHE-5-Me-dC adducts were detected in stomach and intestinal DNA in the range of 0.25-43.71/10(8) bases. After the 4-OHE administration, the amounts of these DNA adducts decreased gradually over 7 days. We also detected 4-OHE-dC in human lung DNA, in the range of 2.6-5.9/10(9) bases. No difference in the 4-OHE adduct levels was detected between smokers and nonsmokers. Our results suggest that 4-OHE-DNA adducts are formed by endogenous as well as environmental lipid peroxides.
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http://dx.doi.org/10.1021/tx9003819DOI Listing
March 2010

Oxidative DNA damage in XPC-knockout and its wild mice treated with equine estrogen.

Chem Res Toxicol 2008 May 1;21(5):1120-4. Epub 2008 May 1.

Laboratory of Chemical Biology, Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794-8651, USA.

Long-term hormone replacement therapy with equine estrogens is associated with a higher risk of breast, ovarian, and endometrial cancers. Reactive oxygen species generated through redox cycling of equine estrogen metabolites may damage cellular DNA. Such oxidative stress may be linked to the development of cancers in reproductive organs. Xeroderma pigmentosa complementation group C-knockout ( Xpc-KO) and wild-type mice were treated with equilenin (EN), and the formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) was determined as a marker of typical oxidative DNA damage, using liquid chromatography electrospray tandem mass spectrometry. The level of hepatic 8-oxodG in wild-type mice treated with EN (5 or 50 mg/kg/day) was significantly increased by approximately 220% after 1 week, as compared with mice treated with vehicle. In the uterus also, the level of 8-oxodG was significantly increased by more than 150% after 2 weeks. Similar results were observed with Xpc-KO mice, indicating that Xpc does not significantly contribute to the repair of oxidative damage. Oxidative DNA damage generated by equine estrogens may be involved in equine estrogen carcinogenesis.
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http://dx.doi.org/10.1021/tx700428mDOI Listing
May 2008

Isolation and identification of xenobiotic aryl hydrocarbon receptor ligands in dyeing wastewater.

Environ Sci Technol 2007 Jan;41(2):652-7

Department of Technology and Ecology, Graduate School of Global Environmental Studies, Kyoto University, Sakyo-Ku Yoshida-Honmachi, Kyoto 606-8501, Japan.

Dyeing wastewater collected in Kyoto city, Japan, was investigated for the occurrence of aryl hydrocarbon receptor (AhR) ligands by using an AhR-responsive reporter gene assay. Concentrated extracts of wastewater samples elicited a dose-dependent increase in AhR ligand activity, and several hydrophobic HPLC fractions of the extracts were highly effective in inducing AhR ligand activity. Three potential AhR ligands were isolated from these fractions and identified to be Disperse Red 92, Disperse Yellow 64, and 3'-hydroxybenzo[b]quinophthalone by using HPLC and LC-MS/MS. Disperse Red 92, which has also been detected in the treated effluent from a sewage plant receiving the wastewater, is an anthraquinone disperse dye showing weak AhR binding affinity in the assay. Disperse Yellow 64 and 3'-hydroxybenzo[b]quinophthalone are quinoline disperse dyes capable of activating the AhR at nanomolar concentrations. In particular, Disperse Yellow 64 is a highly potent AhR ligand that was 3 times more effective in inducing AhR ligand activity than beta-naphthoflavone in the assay. Quinoline disperse dyes are suggested to be a new class of xenobiotic AhR ligands which pose a danger to aquatic biota and human health.
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http://dx.doi.org/10.1021/es061500gDOI Listing
January 2007
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