@article{murrell_gibson_2011, title={Brevetoxin 2 alters expression of apoptotic, DNA damage, and cytokine genes in Jurkat cells}, volume={30}, number={3}, journal={Human & Experimental Toxicology}, author={Murrell, R. N. and Gibson, J. E.}, year={2011}, pages={182–191} } @article{murrell_gibson_2009, title={Brevetoxins 2, 3, 6, and 9 show variability in potency and cause significant induction of DNA damage and apoptosis in Jurkat E6-1 cells}, volume={83}, ISSN={["1432-0738"]}, DOI={10.1007/s00204-009-0443-x}, abstractNote={Brevetoxins (PbTx) are potent lipid soluble polyether neurotoxins produced by the marine dinoflagellate Karenia brevis, an organism linked to periodic red tide blooms. Brevetoxins exert their toxicity by interacting with neurotoxin receptor site five associated with domain IV of the alpha subunit of the voltage gated sodium channel. Brevetoxin binding to tissues that contain voltage gated sodium channels on excitable cells results in membrane depolarization, repetitive firing, and increase in sodium currents. Brevetoxins have been linked to deaths in marine mammals, which are exposed through ingestion of organisms harboring high brevetoxin concentrations and through the inhalation of aerosolized brevetoxins. Humans are also at risk, primarily through respiratory exposure which can result in a severe inflammatory response. The purpose of this study was to determine the effect of four brevetoxins on Jurkat E6-1 cell proliferation, to assess their variability in potency, genotoxicity, and to determine if brevetoxin causes cell death, specifically through an apoptotic or necrotic mechanism. PbTx 2, 3, 6, and 9 were tested at concentrations of 10(-4)-10(-12) M to determine the IC(50) values and effect on cell proliferation. The IC(50) concentration was then used in the single cell gel electrophoresis assay to determine genotoxicity. The ability to induce apoptosis was then assessed with the Vybrant apoptosis assay, caspase activation assays and PARP cleavage. Results from the cellular proliferation assays demonstrated that high doses of PbTxs inhibit the ability of Jurkat cells to proliferate while lower doses caused an increase in proliferation and that PbTx2 is the most cytotoxic brevetoxin followed by brevetoxins 6, 3, and 9. Brevetoxins 2, 3, and 6 all caused significant DNA damage. A 4 h exposure to brevetoxins 2, 3, 6, and 9 at values close to the IC(50) values resulted in apoptosis positive staining in Jurkat E6-1 cells. High doses of brevetoxins 2 and 6 resulted in activation of caspases 3/7 and 8 and cleavage of poly (ADP-ribose) polymerase (PARP). The conclusions are that brevetoxins affect cell proliferation in a dose-dependent fashion, are genotoxic, and cause cell death through an apoptotic mechanism.}, number={11}, journal={ARCHIVES OF TOXICOLOGY}, author={Murrell, Rachel N. and Gibson, James E.}, year={2009}, month={Nov}, pages={1009–1019} } @article{kim_dix_thompson_murrell_schmid_gallagher_rockett_2007, title={Effects of storage, RNA extraction, genechip type, and donor sex on gene expression profiling of human whole blood}, volume={53}, ISSN={["0009-9147"]}, DOI={10.1373/clinchem.2006.078436}, abstractNote={Abstract Background: Gene expression profiling of whole blood may be useful for monitoring toxicological exposure and for diagnosis and monitoring of various diseases. Several methods are available that can be used to transport, store, and extract RNA from whole blood, but it is not clear which procedures alter results. In addition, characterization of interindividual and sex-based variation in gene expression is needed to understand sources and extent of variability. Methods: Whole blood was obtained from adult male and female volunteers (n = 42) and stored at various temperatures for various lengths of time. RNA was isolated and RNA quality analyzed. Affymetrix GeneChips (n = 23) were used to characterize gene expression profiles (GEPs) and to determine the effects on GEP of storage conditions, extraction techniques, types of GeneChip, or donor sex. Hierarchical clustering and principal component analysis were used to assess interindividual differences. Regression analysis was used to assess the relative impact of the studied variables. Results: Storage of blood samples for >1 week at 4 °C diminished subsequent RNA quality. Interindividual GEP differences were seen, but larger effects were observed related to RNA extraction technique, GeneChip, and donor sex. The relative importance of the variables was as follows: storage < genechip < extraction technique < donor sex. Conclusion: Sample storage and extraction methods and interindividual differences, particularly donor sex, affect GEP of human whole blood.}, number={6}, journal={CLINICAL CHEMISTRY}, author={Kim, Sung Jae and Dix, David J. and Thompson, Kary E. and Murrell, Rachel N. and Schmid, Judith E. and Gallagher, Jane E. and Rockett, John C.}, year={2007}, month={Jun}, pages={1038–1045} } @article{rockett_narotsky_thompson_thillainadarajah_blystone_goetz_ren_best_murrell_nichols_et al._2006, title={Effect of conazole fungicides on reproductive development in the female rat}, volume={22}, number={4}, journal={Reproductive Toxicology (Elmsford, N.Y.)}, author={Rockett, J. C. and Narotsky, M. G. and Thompson, K. E. and Thillainadarajah, I. and Blystone, C. R. and Goetz, A. K. and Ren, H. and Best, D. S. and Murrell, R. N. and Nichols, H. P. and et al.}, year={2006}, pages={647–658} } @article{kim_dix_thompson_murrell_schmid_gallagher_rockett_2006, title={Gene expression in head hair follicles plucked from men and women}, volume={36}, number={2}, journal={Annals of Clinical and Laboratory Science}, author={Kim, S. J. and Dix, D. J. and Thompson, K. E. and Murrell, R. N. and Schmid, J. E. and Gallagher, J. E. and Rockett, J. C.}, year={2006}, pages={115–126} } @article{barton_tang_sey_stanko_murrell_rockett_dix_2006, title={Metabolism of myclobutanil and triadimefon by human and rat cytochrome P450 enzymes and liver microsomes}, volume={36}, ISSN={["1366-5928"]}, DOI={10.1080/00498250600821292}, abstractNote={Metabolism of two triazole-containing antifungal azoles was studied using expressed human and rat cytochrome P450s (CYP) and liver microsomes. Substrate depletion methods were used due to the complex array of metabolites produced from myclobutanil and triadimefon. Myclobutanil was metabolized more rapidly than triadimefon, which is consistent with metabolism of the n-butyl side-chain in the former and the t-butyl group in the latter compound. Human and rat CYP2C and CYP3A enzymes were the most active. Metabolism was similar in microsomes prepared from livers of control and low-dose rats. High-dose (115 mg kg−1 day−1 of triadimefon or 150 mg kg−1 day−1 of myclobutanil) rats showed increased liver weight, induction of total CYP, and increased metabolism of the two triazoles, though the apparent Km appeared unchanged relative to the control. These data identify CYP enzymes important for the metabolization of these two triazoles. Estimated hepatic clearances suggest that CYP induction may have limited impact in vivo.}, number={9}, journal={XENOBIOTICA}, author={Barton, H. A. and Tang, J. and Sey, Y. M. and Stanko, J. P. and Murrell, R. N. and Rockett, J. C. and Dix, D. J.}, year={2006}, month={Sep}, pages={793–806} } @article{ekman_keun_eads_furnish_rockett_dix_2006, title={Metabolomic evaluation of rat liver and testis to characterize the toxicity of triazole fungicides}, volume={2}, ISSN={["1573-3890"]}, DOI={10.1007/s11306-006-0020-8}, number={2}, journal={METABOLOMICS}, author={Ekman, Drew R. and Keun, Hector C. and Eads, Charles D. and Furnish, Carrie M. and Rockett, John C. and Dix, David J.}, year={2006}, month={Jun}, pages={63–73} }