title: Dioxin toxicity, aryl hydrocarbon receptor signaling, and apoptosis-persistent pollutants affect programmed cell death.
abstract: Exogenous ligands of the aryl hydrocarbon receptor (AhR) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related substances are highly toxic pollutants ubiquitously present in the environment. They cause a variety of toxic effects to different organs and tissues. Among other effects, TCDD exposure to laboratory animals leads to thymus atrophy and immunosuppression on the one hand, and to tumor formation on the other. Apoptosis appears to be involved in both these toxic effects: AhR activation by TCDD was discussed to induce apoptosis of immune cells, leading to the depletion of thymocytes and ultimately immunosuppression. This mechanism could help to explain the highly immunotoxic actions of TCDD but it is nevertheless under debate whether this is the mode of action for immunosuppression by this class of chemical substances. In other cell types, especially liver cells, TCDD inhibits apoptosis induced by genotoxic treatment. In initiation-promotion studies, TCDD was shown to be a potent liver tumor promoter. Among other theories it was hypothesized that TCDD acts as a tumor promoter by preventing initiated cells from undergoing apoptosis. The exact mechanisms of apoptosis inhibition by TCDD are not fully understood, but both in vivo and in vitro studies consistently showed an involvement of the tumor suppressor p53 in this effect. Various strings of evidence have been established linking apoptosis to the detrimental effects of exogenous activation of the AhR. Within this article, studies elucidating the effects of TCDD and related substances on apoptosis signaling, be it inducing or repressing, is to be reviewed.
authors.affiliation: Institute of Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Chopra
authors.forename: Dieter
authors.initials: D
authors.lastname: Schrenk
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002460:Cell Line; D004147:Dioxins / Q000378:metabolism / Q000633:toxicity*; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D004147:Dioxins; D004785:Environmental Pollutants; D018336:Receptors, Aryl Hydrocarbon; D016159:Tumor Suppressor Protein p53