Dioxin and the AH Receptor: Synergy of Discovery

Why the interest in dioxins, a group of structurally related chemicals which have a common mechanism of action, a common spectrum of biological responses and are environmentally and biologically persistent? A plethora of effects have been reported in people, wildlife, and domestic animals since chloracne was first described in 1899. Cattle, horses, sheep, and chickens have all been shown to be affected during poisoning episodes with polychlorinated byphenyls (PCBs). Fish, birds, and marine mammals have shown adverse outcomes, such as loss of reproduction and immune suppression, at environmental levels. And in the laboratory, species from all vertebrate classes have been used to study the biological effects from exposure to dioxins [1]. While chloracne is diagnostic of poisoning by dioxins, it is only associated with high levels of exposure. However, industrial accidents such as in Nitro, West Virginia, in 1949, Seveso, Italy in 1976, the polybrominated biphenyl (PBB) flame retardant poisoning in Michigan in 1973, and the Binghamton office building fire in 1981, all resulted in some chloracne. In addition, other human poisonings, such as that due to PCB/polychorinated dibenzofuran (PCDF) contaminated rice oil in Japan in 1968 ("Yusho") and Taiwan in 1979 ("Yucheng"), demonstrated a wide range of toxic effects, both on those who ingested the contaminated oil and on their children born afterwards. Intentional poisoning by 2,3,7,8-tetrachloridibenzo-p-dioxin (TCDD), the most toxic polychlorinated dibenzo-p-dioxin (PCDD) congener, occurred to five people in Vienna in 1999, and to the Ukrainian President in 2004 [2].