The Synthesis Core directly supports the research function of the University of lowa SBRP research program (isbrp) by providing PCB exposure mixtures as well as individual PCB congeners and PCB metabolites.
Specific Aim 1 is the maintenance of PCB mixtures and the preparation/maintenance of analytical standards. The Synthesis Core will serve as a repository for technical PCB mixtures (e.g., Aroclors 1242 and 1254) and a synthetic PCB mixture that approximates the average PCB profile found in Chicago air. In addition, the Synthesis Core will maintain analytical standards that are developed in close collaboration with the Analytical Core from pure PCB/PCB metabolites.
Specific Aim 2 is the synthesis of PCB congeners for use with the in vitro and in vivo studies of Research Projects #1, #2 and # 5. These PCB congeners will also be available to the Analytical Core for the preparation of analytical and quality control/assurance standards.
Specific Aim 3 is the synthesis of methoxylated and hydroxylated PCB metabolites. Hydroxylated PCB metabolites will be used by Projects #1, #2, #3, and #5 for in vitro and in vivo studies. Both the hydroxylated and methoxylated PCB derivatives will also be provided to the Analytical Core as analytical standards for the identification and quantification of (unknown) metabolites.
Specific Aim 4 encompasses the synthesis of miscellaneous compounds for the isbrp, including PCB quinones (Projects #1, #2 and #3), PCB glutathione/N-acetyl cysteine conjugates (Project #1), PCB immunogens (Project #1) and PCB sulfates (Project #3). The Synthesis Core will also provide diazomethane as derivatization agent as part of this Aim. This effort indirectly supports Projects #1, #2, #4, #5 and #6. All compounds will be synthesized, if necessary in large (gram) quantities, with straightforward synthetic approaches that are well established at the University of lowa. Drawing on their extensive experience with the synthesis of organohalogen compounds. Synthesis Core staff will be able to synthesize every compound of interest to the individual Research Projects.
|Uwimana, Eric; Li, Xueshu; Lehmler, Hans-Joachim (2018) Human Liver Microsomes Atropselectively Metabolize 2,2',3,4',6-Pentachlorobiphenyl (PCB 91) to a 1,2-Shift Product as the Major Metabolite. Environ Sci Technol 52:6000-6008|
|Herkert, Nicholas J; Hornbuckle, Keri C (2018) Effects of room airflow on accurate determination of PUF-PAS sampling rates in the indoor environment. Environ Sci Process Impacts 20:757-766|
|Herkert, Nicholas J; Spak, Scott N; Smith, Austen et al. (2018) Calibration and evaluation of PUF-PAS sampling rates across the Global Atmospheric Passive Sampling (GAPS) network. Environ Sci Process Impacts 20:210-219|
|Dhakal, Kiran; Gadupudi, Gopi S; Lehmler, Hans-Joachim et al. (2018) Sources and toxicities of phenolic polychlorinated biphenyls (OH-PCBs). Environ Sci Pollut Res Int 25:16277-16290|
|Enayah, Sabah H; Vanle, Brigitte C; Fuortes, Laurence J et al. (2018) PCB95 and PCB153 change dopamine levels and turn-over in PC12 cells. Toxicology 394:93-101|
|Klinefelter, Kelsey; Hooven, Molly Kromme; Bates, Chloe et al. (2018) Genetic differences in the aryl hydrocarbon receptor and CYP1A2 affect sensitivity to developmental polychlorinated biphenyl exposure in mice: relevance to studies of human neurological disorders. Mamm Genome 29:112-127|
|Gourronc, Francoise A; Robertson, Larry W; Klingelhutz, Aloysius J (2018) A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor. Environ Sci Pollut Res Int 25:16481-16492|
|Alam, Sinthia; Carter, Gwendolyn S; Krager, Kimberly J et al. (2018) PCB11 Metabolite, 3,3'-Dichlorobiphenyl-4-ol, Exposure Alters the Expression of Genes Governing Fatty Acid Metabolism in the Absence of Functional Sirtuin 3: Examining the Contribution of MnSOD. Antioxidants (Basel) 7:|
|Li, Xueshu; Holland, Erika B; Feng, Wei et al. (2018) Authentication of synthetic environmental contaminants and their (bio)transformation products in toxicology: polychlorinated biphenyls as an example. Environ Sci Pollut Res Int 25:16508-16521|
|Sethi, Sunjay; Keil, Kimberly P; Lein, Pamela J (2018) 3,3'-Dichlorobiphenyl (PCB 11) promotes dendritic arborization in primary rat cortical neurons via a CREB-dependent mechanism. Arch Toxicol 92:3337-3345|
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