Different susceptibility of mouse tissues to porphyrogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin.
The porphyrogenic effect of chronic administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (25 micrograms/kg/week) to male C57BL/6 mice was evaluated through quantitative and qualitative analysis of the porphyrins accumulated and of porphyrinogen carboxylase activity in liver, kidney, spleen, brain and erythrocytes. The liver was the principal site of action, both for porphyrin accumulation and for enzyme inhibition, with kidney next, whereas brain and erythrocytes were unaffected. In the spleen, despite unchanged formation of total products of uroporphyrinogen III decarboxylation, both an increase and a decrease of coproporphyrinogen formation were observed, the decrease being concomitant with a higher accumulation of tissue porphyrins. When a response to TCDD was found, the formation of the products of decarboxylaction of uroporphyrinogen III were affected to different extents. The pattern of enzyme inhibition paralleled data reported in the literature regarding tissue distribution of TCDD and indicated that TCDD porphyria is a suitable experimental model for the human 'sporadic' type of porphyria cutanea tarda (PCT).
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003653:Decarboxylation; D004147:Dioxins / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011166:Porphyrins / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution; D014577:Uroporphyrinogens / Q000378:metabolism
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D011166:Porphyrins; D014577:Uroporphyrinogens; D002262:Carboxy-Lyases; C022430:porphyrinogen carboxy-lyase