The goal of this proposal is to develop precision cut liver slice culture into a tool for the study of interactive hepatotoxicology. Our studies will concentrate on specific pairs chosen from a group of metal(oids) [As, Cd, Hg, Pb, Se] and a group of halogenated hydrocarbons [carbon tetrachloride, chloroform, trichloroethylene, chlorobenzene, dichlorobenzenes] known to be present at chemical waste sites and with past evidence of indications of interactive toxicity. Three exposure modes will be utilized: one in which both toxicans are administered in vivo, secondly a mode in which one of the toxicants is administered to the intact animal and consecutively the other to liver slices produced from the preexposed animal and finally a mode in which both toxicants are either simultaneously or consecutively added to cultured liver slices. This latter mode is also applied to human tissue with the hope to correlate in vitro with in vivo data in the rat and to predict from in vitro human data interactive hepatotoxicology in exposed human populations. Toxic endpoints are determined with general viability assays applicable to all three exposure modes. Mechanisms of interactive toxicity will be investigated by probing a number of cellular biochemical parameters indicative of: cellular energy status, covalent binding of reactive intermediates generated from the organic toxicant, cell membrane integrity, cellular macromolecule synthesis membrane transport phenomena, deleterious effects of active oxygen species, biotransformation pathways, cellular glutathione status and abnormal cellular architecture.

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University of Arizona
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Pu, Mengjie; Guan, Zeyu; Ma, Yongwen et al. (2018) Synthesis of iron-based metal-organic framework MIL-53 as an efficient catalyst to activate persulfate for the degradation of Orange G in aqueous solution. Appl Catal A Gen 549:82-92
Brusseau, Mark L; Guo, Zhilin (2018) The integrated contaminant elution and tracer test toolkit, ICET3, for improved characterization of mass transfer, attenuation, and mass removal. J Contam Hydrol 208:17-26
Valentín-Vargas, Alexis; Neilson, Julia W; Root, Robert A et al. (2018) Treatment impacts on temporal microbial community dynamics during phytostabilization of acid-generating mine tailings in semiarid regions. Sci Total Environ 618:357-368
Brusseau, Mark L (2018) Assessing the potential contributions of additional retention processes to PFAS retardation in the subsurface. Sci Total Environ 613-614:176-185
Delikhoon, Mahdieh; Fazlzadeh, Mehdi; Sorooshian, Armin et al. (2018) Characteristics and health effects of formaldehyde and acetaldehyde in an urban area in Iran. Environ Pollut 242:938-951
Hammond, Corin M; Root, Robert A; Maier, Raina M et al. (2018) Mechanisms of Arsenic Sequestration by Prosopis juliflora during the Phytostabilization of Metalliferous Mine Tailings. Environ Sci Technol 52:1156-1164
Yan, Ni; Zhong, Hua; Brusseau, Mark L (2018) The natural activation ability of subsurface media to promote in-situ chemical oxidation of 1,4-dioxane. Water Res 149:386-393
Madeira, Camila L; Field, Jim A; Simonich, Michael T et al. (2018) Ecotoxicity of the insensitive munitions compound 3-nitro-1,2,4-triazol-5-one (NTO) and its reduced metabolite 3-amino-1,2,4-triazol-5-one (ATO). J Hazard Mater 343:340-346
Liu, Pengfei; Rojo de la Vega, Montserrat; Sammani, Saad et al. (2018) RPA1 binding to NRF2 switches ARE-dependent transcriptional activation to ARE-NRE-dependent repression. Proc Natl Acad Sci U S A 115:E10352-E10361
Thomas, Andrew N; Root, Robert A; Lantz, R Clark et al. (2018) Oxidative weathering decreases bioaccessibility of toxic metal(loid)s in PM10 emissions from sulfide mine tailings. Geohealth 2:118-138

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