Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology

Abstract

A highly persistent trace environmental contaminant and one of the most potent toxicants known is dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin or TCDD). TCDD induces a broad spectrum of biological responses, including induction of cytochrome P-450 1A1 (CYP1A1), disruption of normal hormone signaling pathways, reproductive and developmental defects, immunotoxicity, liver damage, wasting syndrome, and cancer. Its classification was upgraded from "possible human carcinogen" (group 2B) to "human carcinogen" (group 1) by the International Agency for Research on Cancer (IARC) in 1997. Exposure to TCDD may also cause changes in sex ratio, and tumor promotion in other animals. Because of the growing public and scientific concern, toxicological studies have been initiated to analyze the short- and long-term effects of dioxin. TCDD brings about a wide variety of toxic and biochemical effects via aryl hydrocarbon receptor (AhR)-mediated signaling pathways. Essential steps in this adaptive mechanism include AhR binding of ligand in the cytoplasm of cells associated with two molecules of chaperone heatshock protein (Hsp90) and AhR interactive protein, translocation of the receptor to the nucleus, dimerization with the Ah receptor nuclear translocator, and binding of this heterodimeric transcription factor (present in CYP1A) to dioxin-responsive elements upstream of promoters that regulate the expression of genes involved in xenobiotic metabolism.

MicroRNA‐132 suppresses autoimmune encephalomyelitis by inducing cholinergic anti‐inflammation: A new Ahr‐based exploration

“…The aryl hydrocarbon receptor (Ahr) is a ligand-dependent transcription factor activated by a long list of exogenous ligands including 2,3,7, [1] and 3-methylcholanthrene [2]. Ahr has been shown to mediate the mechanisms that underlie environmental and immunotoxicity [3].…”

“…Ahr has been shown to mediate the mechanisms that underlie environmental and immunotoxicity [3]. Therefore, Ahr represents a fascinating link between the environment and the immune system.…”

Atmospheric polychlorinated biphenyls in Indian cities: Levels, emission sources and toxicity equivalents

“…Some dioxin-like PCBs (dl-PCBs) are of particular toxicological concern. 4 coplanar PCBs and 8 mono-ortho-PCBs share a similar chemical structure and common mechanism of toxic action as that of 7 polychlorinated dibenzo dioxins (PCDDs) and 10 polychlorinated dibenzo furans (PCDFs) (Mandal, 2005;Van den Berg, 2006). dl-PCBs are never found as individual congeners but occur as complex mixtures in air and other environmental media.…”

Determinants of male health: the interaction of biological and social factors

“…For instance, in Serveso, a factory explosion exposed a significant population in central Europe to dioxin [21,22]. For many years later, those couples closest to the explosion had a distortion of the sex ratio of children born such that the number of male children born decreased to approximately 35% compared with an almost 50/50 ratio.…”