Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Uroporphyria and hepatic carcinogenesis induced by polychlorinated biphenyls-iron interaction: absence in the Cyp1a2(-/-) knockout mouse.

Authors: Greaves, Peter; Clothier, Bruce; Davies, Reginald; Higginson, Fiona M; Edwards, Richard E; Dalton, Timothy P; Nebert, Daniel W; Smith, Andrew G

Published In Biochem Biophys Res Commun, (2005 May 27)

Abstract: Aryl hydrocarbon receptor ligands, such as polychlorinated biphenyls (PCBs), cause inhibition of the heme biosynthesis enzyme, uroporphyrinogen decarboxylase; this leads to uroporphyria and hepatic tumors, which are markedly enhanced by iron overload in C57BL/10 and C57BL/6 strains of mice. Cyp1a2(-/-) knockout mice were used to compare the effects of CYP1A2 expression on uroporphyria and liver carcinogenesis. PCBs in the diet (100ppm) of Cyp1a2(+/+) wild-type mice caused hepatic uroporphyria, which was strongly increased by iron-dextran (800mg Fe/kg). In contrast, uroporphyria was not detected in Cyp1a2(-/-) knockout mice, although expression of CYP1A1 and CYP2B10 was greatly induced. After 57 weeks on this diet, hepatic preneoplastic foci and tumors were seen in the Cyp1a2(+/+) mice; numbers and severity were enhanced by iron. No foci or tumors were detected in Cyp1a2(-/-) mice, although evidence for other forms of liver injury was observed. Our findings suggest a link not only between CYP1A2, iron metabolism, and the induction of uroporphyria by PCBs, but also with subsequent hepatocarcinogenesis.

PubMed ID: 15845371 Exiting the NIEHS site

MeSH Terms: Animals; Cytochrome P-450 CYP1A2/genetics; Cytochrome P-450 CYP1A2/metabolism*; Drug Synergism; Environmental Pollutants/toxicity*; Humans; Iron/toxicity*; Liver Neoplasms, Experimental/chemically induced*; Liver Neoplasms, Experimental/enzymology; Mice; Mice, Inbred C57BL; Mice, Knockout; Polychlorinated Biphenyls/toxicity*; Porphyrias, Hepatic/chemically induced*; Porphyrias, Hepatic/enzymology; Porphyrias, Hepatic/pathology; Rats; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.; Uroporphyrins/metabolism

Back
to Top
Last Reviewed: October 07, 2024