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 #
3P42ES010337-03S1
Application #
6667485
Study Section
Special Emphasis Panel (ZES1)
Project Start
2002-04-01
Project End
2003-03-31
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
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

Tripathi, Anupriya; Debelius, Justine; Brenner, David A et al. (2018) The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 15:397-411
Chen, Shujuan; Tukey, Robert H (2018) Humanized UGT1 Mice, Regulation of UGT1A1, and the Role of the Intestinal Tract in Neonatal Hyperbilirubinemia and Breast Milk-Induced Jaundice. Drug Metab Dispos 46:1745-1755
Desai, Archita P; Mohan, Prashanthinie; Roubal, Anne M et al. (2018) Geographic Variability in Liver Disease-Related Mortality Rates in the United States. Am J Med 131:728-734
Ajmera, Veeral; Park, Charlie C; Caussy, Cyrielle et al. (2018) Magnetic Resonance Imaging Proton Density Fat Fraction Associates With Progression of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 155:307-310.e2
Ahmadian, Maryam; Liu, Sihao; Reilly, Shannon M et al. (2018) ERR? Preserves Brown Fat Innate Thermogenic Activity. Cell Rep 22:2849-2859
Tapper, Elliot B; Loomba, Rohit (2018) Nonalcoholic fatty liver disease, metabolic syndrome, and the fight that will define clinical practice for a generation of hepatologists. Hepatology 67:1657-1659
Tripathi, Anupriya; Debelius, Justine; Brenner, David A et al. (2018) Publisher Correction: The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 15:785
Zhang, Yuqin; Nasser, Victoria; Pisanty, Odelia et al. (2018) A transportome-scale amiRNA-based screen identifies redundant roles of Arabidopsis ABCB6 and ABCB20 in auxin transport. Nat Commun 9:4204
Tõldsepp, Kadri; Zhang, Jingbo; Takahashi, Yohei et al. (2018) Mitogen-activated protein kinases MPK4 and MPK12 are key components mediating CO2 -induced stomatal movements. Plant J 96:1018-1035
Li, Zixing; Takahashi, Yohei; Scavo, Alexander et al. (2018) Abscisic acid-induced degradation of Arabidopsis guanine nucleotide exchange factor requires calcium-dependent protein kinases. Proc Natl Acad Sci U S A 115:E4522-E4531

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