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Critical Considerations in the Immunochemical Detection and Quantitation of Antigenic Biomarkers

Biomedical and Environmental Sciences 1991年第1期4卷 113-129页

作者： DEAN W.ROBERTS R.WAYNEBENSON JACK A.HINSON FRED F.KADLUBAR Division of Biochemical Toxicology National Center for Toxicological Research JeffersonDivision of Biochemical Toxicology National Center for Toxicological Research JeffersonDivision of Interdisciplinary Toxicology University of Arkansas for Medical Sciences. Little RockDivision of Biochemical Toxicology National Center for Toxicological Research Jefferson Arkansas 72079-9502Arkansas 72079-9502 Arkansas 72205Arkansas 72079-9502

The formation of covalent adducts as a result of the interaction of metabolically activated chemicals with host macromolecules is a common critical event in mutagenic, carcinogenic, and immunologic phenomena. Because of their antigenicity and their immunogenicity, covalent adducts may be detected using sensitive immunochemical techniques. The immunochemical approaches to biomonitoring and molecular dosimetry of DNA damage are particularly attractive because they allow sensitive quantitation of specific DNA adducts present in small samples and do not rely on the use of radiolabeled adducts. Two examples of biomarker immunoassay development are presented: an avidin/biotin-amplified ELISA for the major DNA adduct of the human bladder carcinogen 4-aminobiphenyl (ABP), and a particle concentration fluorescent immunoassay (PCFIA) for the major protein adduct associated with toxicity by the prototype hepatotoxin acetaminophen. The examples illustrate critical steps in the development of biomarker immunoassays which include selection of the relevant adduct, preparation of an appropriate immunogen, immunization, characterization of antisera, and development of application-specific sample processing techniques for biomarker quantitation. Immunochemical procedures may be combined with other analytical techniques to form hybrid systems which take advantage of both the antigenicity and the physical or chemical properties of a biomarker to achieve greater specificity and/or sensitivity. The future usefulness of these new tools of molecular epidemiology will depend on a compound-by-compound validation of methods and critical evaluation of the biologic importance of the particular antigenic biomarker as an indicator of exposure and as an indicator of risk.

关键词： Critical Considerations in the Immunochemical Detection and Quantitation of Antigenic Biomarkers ABP

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Biomarkers of Human Exposure to Carcinogens: An Overview

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Biomedical and Environmental Sciences 1991年第1期4卷 69-72页

作者： FREDERICK A.BELAND MIRIAM C.POIRIER national center for toxicological research JeffersonNational Cancer Institute Bethesda Arkansas 72079-9502 Maryland 20892

Environmental, occupational, or dietary exposure to certain chemicals has been shown to be associated with carcinogenesis in humans. In the 18th century, for example, Percival Pott (1775) noted a high incidence of scrotal cancer in chimney sweeps, which he attributed to their exposure to soot and a concomitant lack of bathing. Subsequent epidemiological studies have identified a number of additional carcinogenic agents, including aromatic amine-based dyes (Case et al., 1954), cigarette smoke (Wynder and Graham, 1950), asbestos (Doll, 1955), vinyl chloride (Creech and

关键词： An Overview Biomarkers of Human Exposure to Carcinogens

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Critical Considerations in the Immunochemical Detection and Quantitation of Antigenic Biomarkers

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Biomedical and Environmental Sciences 1991年第Z1期 113-129页

作者： DEAN W.ROBERTS,R.WAYNEBENSON,JACK A.HINSON,FRED F.KADLUBAR Division of Biochemical Toxicology national center for toxicological research Jefferson Division of Biochemical Toxicology national center for toxicological research Jefferson Division of Interdisciplinary Toxicology University of Arkansas for Medical Sciences. Little Rock Division of Biochemical Toxicology national center for toxicological research Jefferson Arkansas 72079-9502 Arkansas 72079-9502 Arkansas 72205 Arkansas 72079-9502

关键词： Critical Considerations in the Immunochemical Detection and Quantitation of Antigenic Biomarkers ABP

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Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents

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World Journal of Traditional Chinese Medicine 2020年第1期6卷 12-25页

作者： Xi-Lin Li Xiao-Qing Guo Hai-Rong Wang Tao Chen Nan Mei Division of Genetic and Molecular Toxicology National Center for Toxicological ResearchJeffersonARUSA Tianjin center for New Drug Safety Assessment and research TianjinChina

Aristolochic acid(AA)is a group of structurally related nitrophenanthrene carboxylic acids found in many plants that are widely used by many cultures as traditional herbal *** is a causative agent for Chinese herbs nephropathy,a term replaced later by AA *** indicates that AA is nephrotoxic,genotoxic,and carcinogenic in humans;and it also induces tumors in the forestomach,kidney,renal pelvis,urinary bladder,and lung of rats and ***,plants containing AA have been classified as carcinogenic to humans(Group 1)bytheinternational *** our laboratories,we have conducted a series of genotoxicity and toxicogenomic studies in the rats exposed to AA of 0.1–10 mg/kg for 12 *** results demonstrated that AA treatments induced DNA adducts and mutations in the kidney,liver,and spleen of rats,as well as significant alteration of gene expression in both its target and nontarget *** treatments altered mutagenesis-or carcinogenesis-related microRNA expression in rat kidney and resulted in significant changes in protein expression *** also applied benchmark dose(BMD)modeling to the 3-month AA-induced genotoxicity *** obtained BMDL10(the lower 95%confidence interval of the BMD10 that is a 10%increase over the background level)for AA-induced mutations in the kidney of rats was about 7μg/kg body weight per *** review constitutes an overview of our investigations on AA-induced genotoxicity and toxicogenomic changes including gene expression,microRNA expression,and proteomics;and presents updated information focused on AA-induced genotoxicity in rodents.

关键词： Aristolochic acid benchmark dose genotoxicity mutation toxicogenomics

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Biomarkers of Human Exposure to Carcinogens: An Overview

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Biomedical and Environmental Sciences 1991年第Z1期 69-72页

作者： FREDERICK A.BELAND,MIRIAM C.POIRIER national center for toxicological research Jefferson national Cancer Institute Bethesda Arkansas 72079-9502 Maryland 20892

关键词： An Overview Biomarkers of Human Exposure to Carcinogens

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Metabolomics evaluation of the effects of green tea extract on acetaminophen-induced hepatotoxicity in mice

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中国药理学与毒理学杂志 2013年第3期 463-464页

作者： LU Yi-hong SUN Jin-chun Katya PETROVA YANG Xi James GREENHAW Laura K SCHNACKENBERG William SALMINEN Donna L MENDRICK Richard D BEGER Division of Systems Biology National Center for Toxicological ResearchUS Food and Drug AdministrationJeffersonAR 72079USA Jiangsu Institute for Food and Drug Control PAREXEL international BostonMAUSA

Green tea has a considerable amount of polyphenolic catechins and has been promoted to have beneficial effects on health including protective effects against oxidative ***(APAP) is a widely used analgesic drug which is usually safe at recommended therapeutic doses but overdose can cause acute liver *** studies explored the effects of green tea extract(GTE) on APAP-induced hepatotoxicity using UPLC /MS-and NMR-based metabolomic *** B6C3F1 mice were orally administered GTE under three scenarios either prior to or after a single dose of *** /MS and NMR were employed for metabolomics analysis of the biochemical changes in mice livers with GTE pretreatment 3 h or 3 d prior to APAP exposure or GTE exposure 6 h after *** upon the data,GTE given prior to APAP ameliorated the APAP-induced hepatotoxicity in a dose dependent manner whereas GTE given after APAP potentiated the *** belonging to multiple classes including but not limited to acylcarnitines,energy metabolism,bile acids,and lysoPCs were identified and *** metabolites were significantly altered by APAP exposure alone compared to *** pretreatment generally resulted in these metabolite levels returning to control levels or being less *** given after APAP,however,caused more changes in the metabolites over what was induced by APAP alone indicating more severe *** with biochemistry and histopathology results,the changes in liver metabolites indicated perturbations of fatty acid metabolism,energy metabolism,bile acids metabolism and phospholipids metabolism induced by APAP with differing effects on these metabolites depending upon the time of GTE *** results indicate that the time at which GTE was given highly influenced the severity of APAPinduced *** studies clearly highlight the need to understand the interactions between herbs and other dietary supplements with commonly used ove

关键词： green tea extract acetaminophen hepatotoxicity metabolic profiling

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Antimicrobial resistance in clinically important biofilms

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World Journal of Pharmacology 2015年第1期4卷 31-46页

作者： Fatemeh Rafii Mark E Hart Division of Microbiology National Center for Toxicological ResearchFDA

A biofilm contains a consortium of cohesive bacterial cells forming a complex structure that is a sedentary, but dynamic, community. Biofilms adhere on biotic and abiotic surfaces, including the surfaces of practically all medical devices. Biofilms are reported to be responsible for approximately 60% of nosocomial infections due to implanted medical devices, such as intravenous catheters, and they also cause other foreign-body infections and chronic infections. The presence of biofilm on a medical device may result in the infection of surrounding tissues and failure of the device, necessitating the removal and replacement ofthe device. Bacteria from biofilms formed on medical devices may be released and disperse, with the potential for the formation of new biofilms in other locations and the development of a systemic infection. Regardless of their location, bacteria in biofilms are tolerant of the activities of the immune system, antimicrobial agents, and antiseptics. Concentrations of antimicrobial agents sufficient to eradicate planktonic cells have no effect on the same microorganism in a biofilm. Depending on the microbial consortium or component of the biofilm that is involved, various combinations of factors have been suggested to explain the recalcitrant nature of biofilms toward killing by antibiotics. In this mini-review, some of the factors contributing to antimicrobial resistance in biofilms are discussed.

关键词： Biofilm Bacteria Antimicrobial agent Medical devices Nosocomial infections Resistance

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Chloramination of wastewater effluent: Toxicity and formation of disinfection byproducts

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Journal of Environmental Sciences 2017年第8期29卷 135-145页

作者： Julien Le Roux Michael J.Plewa Elizabeth D.Wagner Maolida Nihemaiti Azra Dad Jean-Philippe Croué LEESU(UMR MA 102) Université Paris-Est–AgroParisTech Department of Crop Sciences the Global Safe Water InstituteUniversity of Illinois at Urbana-Champaign Curtin Water Quality research Centre Department of ChemistryCurtin University US Food and Drug Administration national center for toxicological research

The reclamation and disinfection of waters impacted by human activities（e.g., wastewater effluent discharges） are of growing interest for various applications but has been associated with the formation of toxic nitrogenous disinfection byproducts（N-DBPs）. Monochloramine used as an alternative disinfectant to chlorine can be an additional source of nitrogen in the formation of N-DBPs. Individual toxicity assays have been performed on many DBPs, but few studies have been conducted with complex mixtures such as wastewater effluents. In this work, we compared the cytotoxicity and genotoxicity of wastewater effluent organic matter（Ef OM） before and after chloramination. The toxicity of chloraminated Ef OM was significantly higher than the toxicity of raw Ef OM, and the more hydrophobic fraction（HPO）isolated on XAD-8 resin was more toxic than the fraction isolated on XAD-4 *** DBPs were also isolated on the XAD-8 resin. N-DBPs（i.e., haloacetonitriles or haloacetamides） were responsible for the majority of the cytotoxicity estimated from DBP concentrations measured in the XAD-8 and XAD-4 fractions（99.4% and 78.5%, respectively）.Measured DBPs accounted for minor proportions of total brominated and chlorinated products, which means that many unknown halogenated compounds were formed and can be responsible for a significant part of the toxicity. Other non-halogenated byproducts（e.g.,nitrosamines） may contribute to the toxicity of chloraminated effluents as well.

关键词： Disinfection byproducts Chloramination Toxicity Wastewater XAD resins Haloacetonitriles Haloacetamides

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Protection of Vaginal Epithelial Cells with Probiotic Lactobacilli and the Effect of Estrogen against Infection by <i>Candida albicans</i>

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Open Journal of Medical Microbiology 2012年第3期2卷 54-64页

作者： R. Doug Wagner Shemedia J. Johnson Danielle R. Tucker Microbiology Division National Center for Toxicological Research Jefferson USA

Some probiotic strains of lactobacilli appear to be protective against vulvovaginal candidiasis. The vaginal epithelial cell line (VK2 E6/E7) was used as a model to assess the protective mechanisms of probiotic lactobacilli for cells chal- lenged with Candida albicans. Co-culture of VK2 cells with Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 prior to C. albicans challenge showed reduced adherence of C. albicans to the VK2 cells and inhibition of C. albicans growth. H2O2 concentrations of 0.3 μg/ml, produced by lactobacilli and estrogen-primed VK2 cells, were inhi-bitory to C. albicans growth. C. albicans growth was also inhibited by 10 μg/ml lactic acid. C. albicans infection was increased by 17β-estradiol through induction of hyphal germination. L. reuteri RC-14, but not L. rhamnosus GR-1, H2O2, or lactic acid inhibited estrogen-stimulated hyphal germination. The results of this study support a role for H2O2 and lactic acid from probiotic bacteria in vaginal epithelial protection from candidiasis and a role for 17β-estradiol in the disease by induction of C. albicans hyphal germination.

关键词： Probiotic Epithelial Cells Candidiasis Estrogen Candida albicans

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Significant variations in alternative splicing patterns and expression profiles between human-mouse orthologs in early embryos

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Science China(Life Sciences) 2017年第2期60卷 178-188页

作者： Geng Chen Jiwei Chen Jianmin Yang Long Chen Xiongfei Qu Caiping Shi Baitang Ning Leming Shi Weida Tong Yongxiang Zhao Meixia Zhang Tieliu Shi The center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biology the Institute of Biomedical Sciences and School of Life Sciences East China Normal University center for Pharmacogenomics School of Pharmacy Fudan University national center for toxicological research US Food and Drug Administration Biological Targeting Diagnosis and Therapy research center Guangxi Medical University Department of Ophthalmology West China Hospital Sichuan University

Human and mouse orthologs are expected to have similar biological functions; however, many discrepancies have also been reported. We systematically compared human and mouse orthologs in terms of alternative splicing patterns and expression profiles. Human-mouse orthologs are divergent in alternative splicing, as human orthologs could generally encode more isoforms than their mouse orthologs. In early embryos, exon skipping is far more common with human orthologs, whereas constitutive exons are more prevalent with mouse orthologs. This may correlate with divergence in expression of splicing regulators. Orthologous expression similarities are different in distinct embryonic stages, with the highest in morula. Expression differences for orthologous transcription factor genes could play an important role in orthologous expression discordance. We further detected largely orthologous divergence in differential expression between distinct embryonic stages. Collectively, our study uncovers significant orthologous divergence from multiple aspects, which may result in functional differences and dynamics between human-mouse orthologs during embryonic development.

关键词： ortholog alternative splicing RNA-seq early embryo gene expression

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