Timothy R. Zacharewski

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In an effort to further characterize the mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated toxicity, comprehensive temporal and dose-response microarray analyses were performed on hepatic tissue from immature ovariectomized C57BL/6 mice treated with TCDD. For temporal analysis, mice were gavaged with 30 microg/kg of TCDD or vehicle and(More)
Chronic ingestion of high concentrations of hexavalent chromium [Cr(VI)] in drinking water induces intestinal tumors in mice. To investigate the mode of action (MOA) underlying these tumors, a 90-day drinking water study was conducted using similar exposure conditions as in a previous cancer bioassay, as well as lower (heretofore unexamined) drinking water(More)
In an effort to further characterize conserved and species-specific mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated toxicity, comparative temporal and dose-response microarray analyses were performed on hepatic tissue from immature, ovariectomized Sprague Dawley rats and C57BL/6 mice. For temporal studies, rats and mice were gavaged with(More)
Quantitative risk assessment and the elucidation of mechanisms of toxicity requires computational infrastructure and innovative analysis approaches that systematically consider available data at all levels of biological organization. dbZach (http://dbzach.fst.msu.edu) is a modular relational database with associated data insertion, retrieval, and mining(More)
BACKGROUND The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor (TF) that mediates responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Integration of TCDD-induced genome-wide AhR enrichment, differential gene expression and computational dioxin response element (DRE) analyses further elucidate the hepatic AhR regulatory(More)
BACKGROUND In vitro systems have inherent limitations in their ability to model whole organism gene responses, which must be identified and appropriately considered when developing predictive biomarkers of in vivo toxicity. Systematic comparison of in vitro and in vivo temporal gene expression profiles were conducted to assess the ability of Hepa1c1c7 mouse(More)
Physiological, morphological, and transcriptional alterations elicited by ethynyl estradiol in the uteri of Sprague-Dawley rats and C57BL/6 mice were assessed using comparable study designs, microarray platforms, and analysis methods to identify conserved estrogen signaling networks. Comparative analysis identified 153 orthologous gene pairs that were(More)
BACKGROUND Uterine temporal and dose-dependent histopathologic, morphometric and gene expression responses to the selective estrogen receptor modulator tamoxifen (TAM) were comprehensively examined to further elucidate its estrogen receptor-mediated effects. These results were systematically compared to the effects elicited by the potent estrogen receptor(More)
Studies in rats have demonstrated that modest underlying inflammation can precipitate idiosyncratic-like liver injury from the histamine 2-receptor antagonist, ranitidine (RAN). Coadministration to rats of nonhepatotoxic doses of RAN and the inflammagen, bacterial lipopolysaccharide (LPS), results in hepatocellular injury. We tested the hypothesis that(More)
The B cell, a major component of humoral immunity, is a sensitive target for the immunotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), possibly by rendering cells less responsive to antigenic or mitogenic stimulation. Potential mechanisms of TCDD action on B cells were examined in murine B cell lymphoma cells (CH12.LX) treated with 3 nM TCDD or(More)