Inhibition of apoptosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin depends on protein biosynthesis

Cell Biology and Toxicology
Martin ChopraDieter Schrenk

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic persistent organic pollutant. Most of the toxic effects of TCDD are believed to be mediated by high-affinity binding to the aryl hydrocarbon receptor (AhR) and subsequent effects on gene transcription and protein expression. TCDD causes cancer in multiple tissues in different animal species and is classified as a class 1 human carcinogen. In initiation-promotion studies, TCDD was shown to be a potent liver-tumor promotor. Among other theories it has been hypothesized that TCDD promotes tumor growth by preventing initiated cells from correctly executing apoptosis. In this study, we examined the effects of TCDD on apoptosis induced by UV-C light, ochratoxin A (OTA), and cycloheximide (CHX) in primary rat hepatocytes. Both UV-C light and OTA caused caspase activation and nuclear apoptotic effects. CHX did not activate caspases but nevertheless caused DNA fragmentation and chromatin condensation. TCDD inhibited UV-C light-induced apoptosis and this effect seemed to be dependent on AhR-activation as was shown by employing an AhR antagonist. In contrast to UV-C light-induced apoptosis, TCDD failed to protect primary rat hepatocytes from OTA- or CHX-induced apoptosis. Since ...Continue Reading

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Citations

Jul 7, 2015·Regulatory Toxicology and Pharmacology : RTP·Richard A BeckerRobert A Budinsky
May 3, 2012·Biochemistry Research International·Karine AndreauAida Bouharrour
Jan 23, 2015·Toxicology Mechanisms and Methods·Radhakrishna SuraB Bhaskar Gollapudi
Sep 7, 2014·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Helena Ufelmann, Dieter Schrenk
Feb 9, 2012·Toxicology and Industrial Health·Hasan TurkezMokhtar I Yousef
Oct 29, 2011·Toxicology and Industrial Health·Hasan TürkezMokhtar I Yousef

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