Carbon tetrachloride (CCI{4}) is a superfund toxicant (CERCLA Priority #47) that usually escapes into the environment as a gas. or it is sometimes found in water and soil. The liver is a primary target of the toxicity of CCI4. Exposure to high levels of CCI{4} induces liver damage, inflammation and fibrosis. In healthy people CCI{4} -induced liver injury and fibrosis can reverse when the exposure is discontinued. However, the response of people with underlying liver diseases, such as chronic hepatitis and fatty liver disease, may change, and their livers could be more susceptible to toxicants than healthy livers. Importantly, the health concerns, including chronic liver disease, are often raised regarding vulnerable communities near the Superfund sites. Therefore, the biological response for Superfund toxicants needs to be studied and eariy detection systems need to be developed for identifying these toxicants released into the environment and accumulating in organisms, including the human body. In this context, we will use mouse models with underlying liver diseases, such as Tak1[deltaHEP] mice which have been developed by our laboratory, which mimic human chronic liver disease with liver fibrosis and cancer and mice fed high fat diet that induce obesity and fatty liver disease. Using experimental murine models of liver diseases, we will examine the effect of underlying liver diseases on long-term continuous exposure to CCI{4} with respect to liver fibrosis and cancer. In addition to the evaluation of liver fibrosis by established methodology, we will create a sensitive new detection system for monitoring liver fibrosis using a new fluorescent protein and gene reporter system. This system will also evaluate the effect of another Superfund toxicant in the initiation of liver fibrosis. This project will provide new insights into the effect of environmental CCI{4} exposure on people with underlying liver diseases, including chronic hepatitis and fatty liver. Underlying liver disease is a serious health concern in vulnerable communities, including tribal and low-income border communities that are the targets of our Superfund Research Program. We will share and disseminate our results through the Research Translation and Community Engagement Cores.

Public Health Relevance

Exposure to carbon tetrachloride, a Superfund toxicant, is a health care concern in the Superfund sites and induces liver fibrosis. The goal of this study is to examine whether carbon tetrachloride exposure sustains liver damage and fibrosis in people with underlying diseases and to develop a sensitive new detection system for initiation of liver fibrosis.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-JAB-J (SF))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
La Jolla
United States
Zip Code
Patel, Niraj S; Doycheva, Iliana; Peterson, Michael R et al. (2015) Effect of weight loss on magnetic resonance imaging estimation of liver fat and volume in patients with nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 13:561-568.e1
Seki, Ekihiro; Schwabe, Robert F (2015) Hepatic inflammation and fibrosis: functional links and key pathways. Hepatology 61:1066-79
Fan, Weiwei; Evans, Ronald (2015) PPARs and ERRs: molecular mediators of mitochondrial metabolism. Curr Opin Cell Biol 33:49-54
Yang, Ling; Roh, Yoon Seok; Song, Jingyi et al. (2014) Transforming growth factor beta signaling in hepatocytes participates in steatohepatitis through regulation of cell death and lipid metabolism in mice. Hepatology 59:483-95
Kunz, Hans-Henning; Gierth, Markus; Herdean, Andrei et al. (2014) Plastidial transporters KEA1, -2, and -3 are essential for chloroplast osmoregulation, integrity, and pH regulation in Arabidopsis. Proc Natl Acad Sci U S A 111:7480-5
Schnabl, Bernd; Brenner, David A (2014) Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146:1513-24
Maruo, Yoshihiro; Morioka, Yoriko; Fujito, Hiroshi et al. (2014) Bilirubin uridine diphosphate-glucuronosyltransferase variation is a genetic basis of breast milk jaundice. J Pediatr 165:36-41.e1
Dowding, J M; Song, W; Bossy, K et al. (2014) Cerium oxide nanoparticles protect against A?-induced mitochondrial fragmentation and neuronal cell death. Cell Death Differ 21:1622-32
Roybal, Lacey L; Hambarchyan, Arpi; Meadows, Jason D et al. (2014) Roles of binding elements, FOXL2 domains, and interactions with cJUN and SMADs in regulation of FSH?. Mol Endocrinol 28:1640-55
Nakagawa, Hayato; Umemura, Atsushi; Taniguchi, Koji et al. (2014) ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell 26:331-43

Showing the most recent 10 out of 221 publications