@article{hodgson_wallace_shah_choi_joo_2014, title={Human Variation and Risk Assessment: Microarray and Other Studies Utilizing Human Hepatocytes and Human Liver Subcellular Preparations}, volume={28}, ISSN={["1099-0461"]}, DOI={10.1002/jbt.21534}, abstractNote={The new paradigms proposed for human health risk assessment stress the need for the use of human and human-derived cell lines, and this review summarizes the use of primary human hepatocytes and hepatocyte subcellular preparations for the investigation of the metabolism and metabolic interactions of environmental chemicals. This includes interactions based on inhibition, induction, and activation. The role of cytotoxicity is also considered. The use of hepatocytes and hepatocyte preparations provides especially important information for the investigation of human variation and is summarized. This area is, at present, relatively neglected but will in the future be essential for accurate assessment of human health risk. A detailed summary of an initial attempt to utilize microarray technology for the study of genome-wide effects is included.}, number={1}, journal={JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY}, author={Hodgson, Ernest and Wallace, Andrew D. and Shah, Ruchir R. and Choi, Kyoungju and Joo, Hyun}, year={2014}, month={Jan}, pages={1–10} }
 @article{choi_cope_harms_law_2012, title={Rapid decreases in salinity, but not increases, lead to immune dysregulation in Nile tilapia,Oreochromis niloticus(L.)}, volume={36}, ISSN={0140-7775}, url={http://dx.doi.org/10.1111/j.1365-2761.2012.01417.x}, DOI={10.1111/j.1365-2761.2012.01417.x}, abstractNote={Rapid changes in salinity, as with other environmental stressors, can have detrimental effects on fish and may trigger increased susceptibility to disease. However, the precise mechanisms of these effects are not well understood. We examined the effects of sudden increases or decreases in salinity on teleost immune function using Nile tilapia, Oreochromis niloticus (L.), as the fish model in a battery of bioassays of increasing immune system specificity. Two different salinity experiments were performed: one of increasing salinity (0 to 5, 10 and 20 g L−1) and one of decreasing salinity (20 to 15, 10 and 5 g L−1). Histopathology of anterior kidney, gills, gonads, intestines and liver of exposed fish was performed, but no remarkable lesions were found that were attributable to the salinity treatment regimes. The spleen was removed from each fish for analysis of cytokine expression, and peripheral blood was used for haematology, cortisol and phagocytosis assays. In the increasing salinity experiments, no significant changes were observed in any immune system assays. However, in the decreasing salinity experiments, lymphopenia, neutrophilia and monocytosis were observed in the peripheral blood without modification of the packed cell volume, plasma protein or plasma cortisol levels. Phagocytosis was increased in response to decreases in salinity from 20 g L−1 to 15 g L−1, 10 g L−1 and 5 g L−1, whereas phagocytic index was not significantly altered. Transforming growth factor-β (TGF-β) transcription increased during the same decreases in salinity. However, the TGF-β value at 5 g L−1 was less than those in the 15 and 10 g L−1 salinity treatments. Interleukin-1β (IL-1β) transcription did not significantly respond to either salinity regime. In total, acute salinity changes appeared to trigger reactive dysregulation of the immune response in tilapia, a situation which, when combined with additional co-occurring stressors such as sudden changes in temperature and/or dissolved oxygen, could make fish more susceptible to infectious diseases. Accordingly, these findings may help to explain how sudden environmental changes may initiate disease outbreaks and lead to critical declines in cultured or wild fish populations.}, number={4}, journal={Journal of Fish Diseases}, publisher={Wiley}, author={Choi, K and Cope, W G and Harms, C A and Law, J M}, year={2012}, month={Nov}, pages={389–399} }
 @article{joo_choi_hodgson_2010, title={Human metabolism of atrazine}, volume={98}, ISSN={["1095-9939"]}, DOI={10.1016/j.pestbp.2010.05.002}, abstractNote={Atrazine (ATZ) metabolism by human liver microsomes (HLM), cytochrome P450 (CYP) isoforms, and human liver (HL) S9 fractions, was investigated using HPLC/PDA and LC/MS/MS. CYP-dependent metabolites from pooled HLM are desethylatrazine (DEA), desisopropylatrazine (DIA), 1-hydroxyisopropylatrazine (HIATZ), and 2-hydroxyethyl atrazine (HEATZ). DEA and DIA were major metabolites in pooled HLM. CYP1A2 and 2C19, respectively, were major isoforms for DEA and DIA production. CYP3A4, while less active, is generally at high concentrations, produces both DEA and DIA and is significant. The percent total normalized rates (%TNR) for CYP1A2 and 3A4 in pooled HLM were 63% and 24% for DEA, and 35% and 56% for DIA production. Single donor HLM samples, showed correlations for CYP1A2 (r = 0.92) and 3A4 (r = 0.81) for DEA and DIA production, while variations in production of DEA and DIA were 8.5- and 6.0-fold, respectively. Pooled S9 fractions also mediate glutathione conjugation of atrazine, DEA and DIA.}, number={1}, journal={PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY}, author={Joo, Hyun and Choi, Kyoungju and Hodgson, Ernest}, year={2010}, month={Sep}, pages={73–79} }
 @article{choi_lehmann_harms_law_2007, title={Acute hypoxia-reperfusion triggers immunocompromise in Nile tilapia}, volume={19}, ISSN={["1548-8667"]}, DOI={10.1577/H06-010.1}, abstractNote={Inadequate dissolved oxygen in the aquatic environment is a well-established cause of fish morbidity and mortality. The specific effects of hypoxia on immune function in fish, however, are not well characterized. In this study, the effects of acute hypoxia followed by reoxygenation (rapid tissue reperfusion) as a source of immunocompromise in Nile tilapia Oreochromis niloticus were investigated. Using a precision apparatus developed in our laboratory for hypoxia exposures, a series of assays of increasing specificity for immune function were performed on acutely hypoxia-stressed Nile tilapia: tier I consisted of histopathology, tier II of hematology, plasma chemistry, and determining cortisol concentration, and tier III of determining the phagocytic index and analyzing the expression of the cytokines transforming growth factor-beta (TGF-beta) and interleukin-1beta (IL-1beta). Nile tilapia were exposed to 7% oxygen saturation for 96 h, then tank water was rapidly reoxygenated. Sampling intervals were 48 and 96 h during hypoxia and 12 and 84 h during reperfusion. Histopathology showed no remarkable microscopic abnormalities in lymphoid or other tissues. Lymphopenia and neutrophilia were observed in peripheral blood. Plasma total protein, partial pressure of oxygen, and oxygen saturation were decreased in response to hypoxia. Plasma lipase decreased in response to hypoxia but returned to normal during reperfusion. Phagocytic capability and the phagocytic index decreased during hypoxia and 12 h reperfusion, whereas these values were recovered by 84 h reperfusion. The TGF-beta transcription continued to increase during the exposures, the greatest production being at 12 h reperfusion, whereas IL-1beta transcription decreased in response to hypoxia and reperfusion. We conclude that acute hypoxia triggered an overall downregulation of the immune system in the test fish. This suggests a possible factor in the pathogenesis of disease outbreaks in fish in which repeated, sublethal bouts of environmentally induced hypoxia lead to increased disease susceptibility and individual mortalities rather than massive fish kills.}, number={2}, journal={JOURNAL OF AQUATIC ANIMAL HEALTH}, author={Choi, K. and Lehmann, D. W. and Harms, C. A. and Law, J. M.}, year={2007}, month={Jun}, pages={128–140} }
 @article{joo_choi_rose_hodgson_2007, title={Inhibition of fipronil and nonane metabolism in human liver microsomes and human cytochrome P450 isoforms by chlorpyrifos}, volume={21}, ISSN={["1095-6670"]}, DOI={10.1002/jbt.20161}, abstractNote={Previous studies have established that chlorpyrifos (CPS), fipronil, and nonane can all be metabolized by human liver microsomes (HLM) and a number of cytochrome P450 (CYP) isoforms. However, metabolic interactions between these three substrates have not been described. In this study the effect of either coincubation or preincubation of CPS with HLM or CYP isoforms with either fipronil or nonane as substrate was investigated. In both co- and preincubation experiments, CPS significantly inhibited the metabolism of fipronil or nonane by HLM although CPS inhibited the metabolism of fipronil more effectively than that of nonane. CPS significantly inhibited the metabolism of fipronil by CYP3A4 as well as the metabolism of nonane by CYP2B6. In both cases, preincubation with CPS caused greater inhibition than coincubation, suggesting that the inhibition is mechanism based. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:76–80, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20161}, number={2}, journal={JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY}, author={Joo, Hyun and Choi, Kyoungju and Rose, Randy L. and Hodgson, Ernest}, year={2007}, pages={76–80} }
 @article{choi_joo_rose_hodgson_2006, title={Metabolism of chlorpyrifos and chlorpyrifos oxon by human hepatocytes}, volume={20}, DOI={10.1002/jbt.20145}, abstractNote={The metabolism of chlorpyrifos (CPS) and chlorpyrifos oxon (CPO) by human hepatocytes and human liver S9 fractions was investigated using LC-MS/MS. Cytochrome P450 (CYP)-dependent and phase II-related products were determined following incubation with CPS and CPO. CYP-related products, 3,5,6-trichloro-2-pyridinol (TCP), diethyl thiophosphate, and dealkylated CPS, were found following CPS treatment and dealkylated CPO following CPO treatment. Diethyl phosphate was not identified because of its high polarity and lack of retention with the chromatographic conditions employed. Phase II-related conjugates, including O- and S-glucuronides as well as 11 GSH-derived metabolites, were identified in CPS-treated human hepatocytes, although the O-sulfate of TCP conjugate was found only when human liver S9 fractions were used as the enzyme source. O-Glucuronide of TCP was also identified in CPO-treated hepatocytes. CPS and CPO were identified using HPLC-UV after CPS metabolism by the human liver S9 fraction. However, CPO was not found following treatment of human hepatocytes with either CPS or CPO. These results suggest that human liver plays an important role in detoxification, rather than activation, of CPS.}, number={6}, journal={Journal of Biochemical and Molecular Toxicology}, author={Choi, K. and Joo, H. and Rose, R. L. and Hodgson, E.}, year={2006}, pages={279–291} }