A histochemical and pathological study on the interrelationship between TCDD-induced AhR expression, AhR activation, and hepatotoxicity in mice

H. Chang, Ying Jan Wang, Louis W. Chang, Pinpin Lin

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

The objective of this study was to establish a correlation and interrelationship between aryl hydrocarbon receptor (AhR) and hepatotoxicity induced by TCDD. Young male ICR mice were exposed to TCDD via dermal exposure at doses of 0, 2.5, 25, and 125 ng TCDD twice weekly for 20 wk. Histopathological examination revealed a classic pattern and dose-dependent pathological changes in sinusoidal dilatations, hepatocellular swelling and degeneration, fatty infiltration, and hepatocellular necrosis. Immunochemical staining for AhR also demonstrated that the AhR-positive hepatocytes were centrilobular in location, especially with those cells cuffing the central vein. With exposures to TCDD, the number of AhR-positive cells increased with dose. Furthermore, we also demonstrated all the hepatocytes that exhibited pathological changes (e.g., fatty infiltration or necrosis) were AhR-positive. Depletion in AhR (AhR removal after activation) in many centrilobular hepatocytes, with disappearance of the AhR positive cuffing, was observed in the high TCDD exposed animals. AhR activation was also evident by the increase in CYP 1A2 expression in many centrilobular hepatocytes, especially those exposed to high doses of TCDD. Studies in the past, with experiments performed separately, could only suggest the association of AhR expression and hepatocellular toxicity. By examining the AhR expression, AhR activation (CYP 1A2 expression up regulation), and hepatocellular pathology together, it was possible to correlate these factors in the same animal and even in the same cells. Our finding provided direct evidence on the interaction and causal relationship between AhR activation and hepatic toxicity. Copyright

Original languageEnglish
Pages (from-to)1567-1579
Number of pages13
JournalJournal of Toxicology and Environmental Health - Part A
Volume68
Issue number17-18
DOIs
Publication statusPublished - 2005 Sep 10

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'A histochemical and pathological study on the interrelationship between TCDD-induced AhR expression, AhR activation, and hepatotoxicity in mice'. Together they form a unique fingerprint.

Cite this