Abstract

One aspect of the long-term exposure to toxins is significant alterations in patterns of gene expression. Toxin-related changes in gene regulation may contribute to the profile of illnesses caused by Superfund site toxicants, and can serve as a powerful marker of exposure and biohazard. In assessing hazards arising from Superfund sites, it would be highly desirable to develop cheap and rapid screens for the presence of environmental hazards, for the hazards posed by mixtures of toxins and to test large numbers of field isolates. To detect genes that are up- or down- regulated in response to toxins, we propose to use a gene-trapping approach with beta-lactamase as reporter in cell lines that are relevant to long-term toxicity. Cell lines in which beta-lactamase has trapped a toxin responsive gene will be used to identify trapped genes by RACE. Several tens of these cell lines will be validated for ultra-high-throughput screening assays to predict the biohazard potential of large numbers of samples (approximately 10/5 assays/day) consisting of candidate toxicants. mixtures, and field isolates.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
1P42ES010337-01
Application #
6326956
Study Section
Special Emphasis Panel (ZES1-DPB-D (G3))
Project Start
2000-07-01
Project End
2005-03-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
$175,014
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Dow, Michelle; Pyke, Rachel M; Tsui, Brian Y et al. (2018) Integrative genomic analysis of mouse and human hepatocellular carcinoma. Proc Natl Acad Sci U S A 115:E9879-E9888
Kim, Ju Youn; Garcia-Carbonell, Ricard; Yamachika, Shinichiro et al. (2018) ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P. Cell 175:133-145.e15
Que, Xuchu; Hung, Ming-Yow; Yeang, Calvin et al. (2018) Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice. Nature 558:301-306
Fan, Weiwei; He, Nanhai; Lin, Chun Shi et al. (2018) ERR? Promotes Angiogenesis, Mitochondrial Biogenesis, and Oxidative Remodeling in PGC1?/?-Deficient Muscle. Cell Rep 22:2521-2529
Brouha, Sharon S; Nguyen, Phirum; Bettencourt, Ricki et al. (2018) Increased severity of liver fat content and liver fibrosis in non-alcoholic fatty liver disease correlate with epicardial fat volume in type 2 diabetes: A prospective study. Eur Radiol 28:1345-1355
Hsu, Po-Kai; Takahashi, Yohei; Munemasa, Shintaro et al. (2018) Abscisic acid-independent stomatal CO2 signal transduction pathway and convergence of CO2 and ABA signaling downstream of OST1 kinase. Proc Natl Acad Sci U S A 115:E9971-E9980
Dhar, Debanjan; Antonucci, Laura; Nakagawa, Hayato et al. (2018) Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling. Cancer Cell 33:1061-1077.e6
Febbraio, Mark A; Reibe, Saskia; Shalapour, Shabnam et al. (2018) Preclinical Models for Studying NASH-Driven HCC: How Useful Are They? Cell Metab :
Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H (2018) Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans. Drug Metab Pharmacokinet 33:9-16
Hartmann, Phillipp; Hochrath, Katrin; Horvath, Angela et al. (2018) Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice. Hepatology 67:2150-2166

Showing the most recent 10 out of 404 publications