Induction of mixed-function oxidase by chronic treatment with 2,3,7,8-tetrachloro-dibenzo-p-dioxin in female rats

The effect of a 45-week treatment with different doses of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) (0.01, 0.10 and 1.00 μg/kg/week) was evaluated in female rat liver by determining cytochrome P-450 and b₅ content and the activities of the enzymes cytochrome c reductase, aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (7-ECD); TCDD content in the liver was also measured. Cytochrome b₅ and cytochrome c reductase were unaffected at any of the dose levels and cytochrome P-450 was significantly induced only at the highest TCDD dose, but marked induction of AHH and 7-ECD was apparent when the animals were treated with 0.01 μg/kg/week; a clear dose-response relationship was present in the induction at the 2 lower doses (0.01 and 0.10 μg/kg/week). The amount of TCDD found in lever tissue (1050, 4740 and 30 700 ppt, respectively, for 0.01, 0.10 and 1.00 μg/kg/week) indicated a relatively higher accumulation of this compound at lower doses.