In vitro inhibitory effect on porphyrinogen carboxylyase of liver extracts from TCDD treated mice.

Marked inhibition of porphyrinogen carboxylyase was produced in vitro by cytosol fractions, deproteinized and free of porphyrins, obtained from livers of mice made porphyric by 9 weeks i.p. treatment with 25 micrograms/kg/week of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Inhibition was proportional to the amount of the fraction added, was increased by preincubation in the absence of the substrate and, once established, could not be reversed by dialysis. TCDD itself, added to the control enzyme in the incubation mixture, did not affect enzyme activity up to a concentration of 77 nM, which is 10 times higher than the liver TCDD concentration found after in vivo TCDD treatment.