publication . Article . 2015

Mechanism Profiling of Hepatotoxicity Caused by Oxidative Stress Using Antioxidant Response Element Reporter Gene Assay Models and Big Data.

Marlene Thai Kim; Ruili Huang; Alexander Sedykh; Wenyi Wang; Menghang Xia; Hao Zhu;
Open Access English
  • Published: 01 Sep 2015 Journal: Environmental Health Perspectives, volume 124, issue 5, pages 634-641 (issn: 0091-6765, eissn: 1552-9924, Copyright policy)
  • Publisher: National Institute of Environmental Health Sciences
Abstract
Background: Hepatotoxicity accounts for a substantial number of drugs being withdrawn from the market. Using traditional animal models to detect hepatotoxicity is expensive and time-consuming. Alternative in vitro methods, in particular cell-based high-throughput screening (HTS) studies, have provided the research community with a large amount of data from toxicity assays. Among the various assays used to screen potential toxicants is the antioxidant response element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress and was used to test > 10,000 compounds from the Tox21 program. Objective:...
Subjects
free text keywords: Research, Reporter gene, Response element, Antioxidant Response Elements, Toxicology, Oxidative stress, medicine.disease_cause, medicine, Pharmacology, Biology, Antioxidant, medicine.medical_treatment
65 references, page 1 of 5

Adler, S, Basketter, D, Creton, S, Pelkonen, O, van Benthem, J, Zuang, V. Alternative (non-animal) methods for cosmetics testing: current status and future prospects—2010.. Arch Toxicol. 2011; 85: 367-485 [OpenAIRE] [PubMed]

Allen, TEH, Goodman, JM, Gutsell, S, Russell, PJ. Defining molecular initiating events in the adverse outcome pathway framework for risk assessment.. Chem Res Toxicol. 2014; 27: 2100-2112 [PubMed]

Ankley, GT, Bennett, RS, Erickson, RJ, Hoff, DJ, Hornung, MW, Johnson, RD. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment.. Environ Toxicol Chem. 2010; 29: 730-741 [OpenAIRE] [PubMed]

Attene-Ramos, MS, Miller, N, Huang, R, Michael, S, Itkin, M, Kavlock, RJ. The Tox21 robotic platform for the assessment of environmental chemicals—from vision to reality.. Drug Discov Today. 2013; 18: 716-723 [OpenAIRE] [PubMed]

Baell, JB, Holloway, GA. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays.. J Med Chem. 2010; 53: 2719-2740 [OpenAIRE] [PubMed]

Ben Hassine, S, Arcangioli, B. Tdp1 protects against oxidative DNA damage in non–dividing fission yeast.. EMBO J. 2009; 28: 632-640 [OpenAIRE] [PubMed]

Borduas, N, da Silva, G, Murphy, JG, Abbatt, JPD. Experimental and theoretical understanding of the gas phase oxidation of atmospheric amides with OH radicals: kinetics, products, and mechanisms.. J Phys Chem A. 2015; 119: 4298-4308 [PubMed]

Breiman, L. Random forests.. Mach Learn. 2001; 45: 5-32

Cytotoxic agents.. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics (Brunton LL, Chabner BA, Knollmann BC, eds). 12th ed. 2011: 1677-1730

Chen, M, Borlak, J, Tong, W. Predicting idiosyncratic drug-induced liver injury: some recent advances.. Expert Rev Gastroenterol Hepatol. 2014; 8: 721-723 [PubMed]

Collins, FS, Gray, GM, Bucher, JR. Toxicology. Transforming environmental health protection.. Science. 2008; 319: 906-907 [OpenAIRE] [PubMed]

Biostatistics: A Foundation for Analysis in the Health Sciences. 9th ed.. 2009

Davies, DS, Thorgeirsson, SS. Mechanism of hepatic drug oxidation and its relationship to individual differences in rates of oxidation in man.. Ann NY Acad Sci. 1971; 179: 411-420 [PubMed]

Dix, DJ, Houck, KA, Martin, MT, Richard, AM, Setzer, RW, Kavlock, RJ. The ToxCast program for prioritizing toxicity testing of environmental chemicals.. Toxicol Sci. 2007; 95: 5-12 [OpenAIRE] [PubMed]

Principles of toxicology.. In: Casarett & Doull’s Essentials of Toxicology (Klaassen CD, Watkins JB III, eds). 2nd ed. 2010: 5-19

65 references, page 1 of 5
Abstract
Background: Hepatotoxicity accounts for a substantial number of drugs being withdrawn from the market. Using traditional animal models to detect hepatotoxicity is expensive and time-consuming. Alternative in vitro methods, in particular cell-based high-throughput screening (HTS) studies, have provided the research community with a large amount of data from toxicity assays. Among the various assays used to screen potential toxicants is the antioxidant response element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress and was used to test > 10,000 compounds from the Tox21 program. Objective:...
Subjects
free text keywords: Research, Reporter gene, Response element, Antioxidant Response Elements, Toxicology, Oxidative stress, medicine.disease_cause, medicine, Pharmacology, Biology, Antioxidant, medicine.medical_treatment
65 references, page 1 of 5

Adler, S, Basketter, D, Creton, S, Pelkonen, O, van Benthem, J, Zuang, V. Alternative (non-animal) methods for cosmetics testing: current status and future prospects—2010.. Arch Toxicol. 2011; 85: 367-485 [OpenAIRE] [PubMed]

Allen, TEH, Goodman, JM, Gutsell, S, Russell, PJ. Defining molecular initiating events in the adverse outcome pathway framework for risk assessment.. Chem Res Toxicol. 2014; 27: 2100-2112 [PubMed]

Ankley, GT, Bennett, RS, Erickson, RJ, Hoff, DJ, Hornung, MW, Johnson, RD. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment.. Environ Toxicol Chem. 2010; 29: 730-741 [OpenAIRE] [PubMed]

Attene-Ramos, MS, Miller, N, Huang, R, Michael, S, Itkin, M, Kavlock, RJ. The Tox21 robotic platform for the assessment of environmental chemicals—from vision to reality.. Drug Discov Today. 2013; 18: 716-723 [OpenAIRE] [PubMed]

Baell, JB, Holloway, GA. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays.. J Med Chem. 2010; 53: 2719-2740 [OpenAIRE] [PubMed]

Ben Hassine, S, Arcangioli, B. Tdp1 protects against oxidative DNA damage in non–dividing fission yeast.. EMBO J. 2009; 28: 632-640 [OpenAIRE] [PubMed]

Borduas, N, da Silva, G, Murphy, JG, Abbatt, JPD. Experimental and theoretical understanding of the gas phase oxidation of atmospheric amides with OH radicals: kinetics, products, and mechanisms.. J Phys Chem A. 2015; 119: 4298-4308 [PubMed]

Breiman, L. Random forests.. Mach Learn. 2001; 45: 5-32

Cytotoxic agents.. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics (Brunton LL, Chabner BA, Knollmann BC, eds). 12th ed. 2011: 1677-1730

Chen, M, Borlak, J, Tong, W. Predicting idiosyncratic drug-induced liver injury: some recent advances.. Expert Rev Gastroenterol Hepatol. 2014; 8: 721-723 [PubMed]

Collins, FS, Gray, GM, Bucher, JR. Toxicology. Transforming environmental health protection.. Science. 2008; 319: 906-907 [OpenAIRE] [PubMed]

Biostatistics: A Foundation for Analysis in the Health Sciences. 9th ed.. 2009

Davies, DS, Thorgeirsson, SS. Mechanism of hepatic drug oxidation and its relationship to individual differences in rates of oxidation in man.. Ann NY Acad Sci. 1971; 179: 411-420 [PubMed]

Dix, DJ, Houck, KA, Martin, MT, Richard, AM, Setzer, RW, Kavlock, RJ. The ToxCast program for prioritizing toxicity testing of environmental chemicals.. Toxicol Sci. 2007; 95: 5-12 [OpenAIRE] [PubMed]

Principles of toxicology.. In: Casarett & Doull’s Essentials of Toxicology (Klaassen CD, Watkins JB III, eds). 2nd ed. 2010: 5-19

65 references, page 1 of 5
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publication . Article . 2015

Mechanism Profiling of Hepatotoxicity Caused by Oxidative Stress Using Antioxidant Response Element Reporter Gene Assay Models and Big Data.

Marlene Thai Kim; Ruili Huang; Alexander Sedykh; Wenyi Wang; Menghang Xia; Hao Zhu;