3,4,3′,4′-Tetrachloro Azoxybenzene and Azobenzene: Potent Inducers of Aryl Hydrocarbon Hydroxylase

Abstract

Two unwanted contaminants, 3,4,3',4'-tetrachloroazoxybenzene (TCAOB) and 3,4,3',4'-tetrachloroazobenzene (TCAB), formed in the commercial synthesis of 3,4-dichloroaniline or of herbicides made from 3,4-dichloroaniline, were responsible for three outbreaks of acne among chemical workers. TCAOB and TCAB are approximately isosteric to 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran, two well-known contaminants that cause acne. All four of these agents are potent inducers of hepatic aryl hydrocarbon hydroxylase activity and compete for stereospecific binding sites in the hepatic cytosol, which are thought to be the receptor sites for the induction of this enzyme. Among the chlorinated azoxy and azobenzenes, the potency of a congener to induce aryl hydrocarbon hydroxylase activity correlates with its binding affinity for the hepatic cytosol specific binding sites and its capacity to induce acne; this relation between structure and activity parallels that observed for the chlorinated dibenzo-p-dioxins and dibenzofurans.