Effects of Hexachlorobenzene Feeding and Iron Overload on Enzymes of Haem Biosynthesis and Cytochrome P450 in Rat Liver

1. The effect of hexachlorobenzene feeding on liver δ-aminolaevulinate synthase, uroporphyrinogen decarboxylase and cytochrome P450 was studied at various time-intervals in siderotic and non-siderotic rats. 2. In the non-siderotic group hexachlorobenzene feeding led to a progressive decrease in liver uroporphyrinogen decarboxylase activity, accompanied by a progressive increase in δ-aminolaevulinate synthase activity. Cytochrome P450 concentrations were above normal throughout but fell toward the end of the experiment. 3. Similar but more marked changes were found in the siderotic animals. The fall in uroporphyrinogen decarboxylase activity occurred earlier and was significantly greater in these animals, whereas the increase in δ-aminolaevulinate synthase activity was consistently larger. Liver cytochrome P450 concentration also rose but to a lesser extent than that in the non-siderotic rats. 4. Hexachlorobenzene-induced porphyria would seem to be attributable to inhibition or inactivation of hepatic uroporphyrinogen decarboxylase. Hepatic siderosis has a synergistic effect with hexachlorobenzene on this enzyme and may exert additional effects by promoting cytochrome P450 turnover.