Biological effects of the Sudan dyes: Role of the Ah cytosolic receptor

The hepatic induction of two cytochrome P 1450-mediated activities [aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (ETR)] was studied following the administration of the azo dyes Sudan I, II, III and IV. When using Ah-responsive C57BL/6J mice, Sudan dye II proved to be quite potent as an inducer causing almost maximal induction at doses as low as 40 mg/kg (1.4 μmoles/kg body weight); Sudan dyes I, III and IV caused one-half the maximal induction at four times that dose. In contrast, none of these compounds caused induction of AHH or ETR in the Ah-nonresponsive DBA/2J animals. When the dyes were given to B6D2F 1 × D2 backcross progeny, a strict correlation with the presence of the Ah b allele and the inducibility of AHH and ETR was observed. When these compounds were examined as agonists for the Ah cytosolic receptor by their capacity to replace [ 3H]2,3,7,8-tetrachlorodibenzo- p-dioxin binding, Sudan dye II was substantially more effective than Sudan dyes I, III and IV. When four repeated doses of Sudan dye II were administered intraperitoneally to Ah-responsive C57BL/6J mice and Ah-nonresponsive DBA/2J mice, Sudan dye II-induced immunotoxicity was markedly greater in C57BL/6J compared to DBA/2J mice.