PMID: 9664232Jul 17, 1998Paper

Use of c-Src and c-Fos knockout mice for the studies on the role of c-Src kinase signaling in the expression of toxicity of TCDD

Journal of Biochemical and Molecular Toxicology
E EnanF Matsumura

Abstract

Previously, we reported that several of the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were not fully expressed in c-src -/- and -/+ mice (1). In the current study, we studied the basic molecular mechanism of their differential responses. First, we could show that chemical inhibition of c-src kinase could produce practically the same phenomenon of reduced toxicity of TCDD in wild-type mice cotreated with geldanamycin, a specific chemical inhibitor known to suppress c-src kinase. Second, we established that the level of the Ah receptor associated with c-src kinase (2) is indeed low in c-src deficient mice as well as geldanamycin-treated mice. We could show, at the same time, that the effect of c-src deficiency on the toxicity of TCDD is very selective; that is, despite the reduction of many of its toxic signs, the enlargement of liver, induction of cytochrome P450, and other drug-metabolizing enzymes took place normally in those c-src-deficient mice. Apparently, induction of these detoxification enzymes are independent of c-src-mediated pathway. Based on the known signaling pathways of c-src, we tested c-fos-deficient mice and found that some of the c-src-dependant toxic signs of TCDD such as thymic atrophy and ...Continue Reading

Citations

Sep 6, 2002·Chemico-biological Interactions·Alvaro PugaCornelis Elferink
Feb 10, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Donatella CarpiRoberta Pastorelli
May 15, 2001·Toxicology and Applied Pharmacology·P L LukinmaaS Alaluusua
Jun 11, 2005·The Journal of Biological Chemistry·Sonia Mulero-NavarroPedro M Fernández-Salguero
Oct 8, 2005·Journal of Cellular Biochemistry·Jennifer L Marlowe, Alvaro Puga
Sep 29, 2004·Cellular Signalling·Maria Backlund, Magnus Ingelman-Sundberg

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