Uroporphyria in mice: thresholds for hepatic CYP1A2 and iron

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
N GormanP R Sinclair

Abstract

In mice treated with 5-aminolevulinic acid (ALA) and polyhalogenated aromatic compounds, the levels of both hepatic cytochrome P450 (CYP)1A2 and iron-which can be quite different among inbred strains-are critical in causing experimental uroporphyria. Here we investigate the development of uroporphyria as a function of CYP1A2 and iron levels in the liver of mice having a common C57BL/6 genetic background. We compared Cyp1a2(-/-) knockout mice, Cyp1a2(+/-) heterozygotes, Cyp1a2(+/+) wild type, and Cyp1a2(+/+) mice pretreated with a low dose of 3,3',4,4',5-pentachlorobiphenyl (PCB126) (4 microg/kg). Cyp1a2(+/-) mice contain about 60% of the hepatic CYP1A2 content of Cyp1a2(+/+) mice, and the PCB126-pretreated Cyp1a2(+/+) mice have about twice the wild-type levels of CYP1A2. ALA- and iron-treated Cyp1a2(+/+) mice are known to accumulate hepatic uroporphyrin; this accumulation was increased 7-fold by pretreatment with the low dose of PCB126. ALA- and iron-treated Cyp1a2(+/-) heterozygote mice accumulated no uroporphyrin in 4 weeks, but by 8 weeks accumulated significant amounts of uroporphyrin. As previously reported, the ALA- and iron-treated Cyp1a2(-/-) knockout mouse has no CYP1A2 and exhibits no detectable uroporphyrin accumulat...Continue Reading

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Citations

May 28, 2004·Journal of Biochemical and Biophysical Methods·Martin A GrundyGlenn S Gerhard
Sep 6, 2003·Alcohol·Herbert L BonkovskyYing Shan
Oct 6, 2005·Environmental Health Perspectives·Pierre AyotteDaria Pereg
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·John D PhillipsJames P Kushner
Sep 26, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Michael R FranklinJames P Kushner
Oct 29, 2008·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Kenzi NakanoShoichi Fujita
Jul 7, 2007·Critical Reviews in Toxicology·Yasuhiro Masubuchi, Toshiharu Horie
Sep 24, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nadia GormanPeter R Sinclair
Sep 2, 2011·Blood Cells, Molecules & Diseases·John D PhillipsMichael R Franklin
May 1, 2007·Toxicology and Applied Pharmacology·Nadia GormanPeter R Sinclair
Sep 15, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nadia GormanPeter R Sinclair
Dec 26, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nadia GormanPeter R Sinclair
Apr 6, 2005·Toxicology and Applied Pharmacology·Silvia C Billi de CatabbiAdriana C Cochón
Nov 1, 2005·Environmental Toxicology and Pharmacology·Michael R FranklinJames P Kushner
Apr 23, 2005·Biochemical and Biophysical Research Communications·Peter GreavesAndrew G Smith
Jan 24, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Peter R SinclairGlenn S Gerhard
May 22, 2010·Transplant Infectious Disease : an Official Journal of the Transplantation Society·T WeberG Behre
Jan 27, 2010·Chemical Research in Toxicology·Andrew G Smith, George H Elder

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