Uroporphyria development in cultured chick embryo fibroblasts long-term treated with chloramphenicol and ethidium bromide.
Long-term chloramphenicol- and ethidium bromide-treated chick embryo fibroblasts synthesize large amounts of porphyrins from exogenously added delta-aminolevulinic acid. The porphyrins consist mainly of uro- and heptacarboxyporphyrins and are retained within cells. Uroporphyria development is a time-dependent process which accompanies a step-wise decrease in the capacity of the mitochondrial respiratory chain. Upon removal of chloramphenicol from the medium, the pattern of porphyrin production readily returns to normal (mainly proto- and coproporphyrins found in the medium) while ethidium bromide-treated cells remain uroporphyric. The results suggest that impairment of mitochondrial functions in chicken by xenobiotics leads to uroporphyria development.
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002701:Chloramphenicol / Q000494:pharmacology*; D004996:Ethidium / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects; D011166:Porphyrins / Q000096:biosynthesis*; D013997:Time Factors; D014575:Uroporphyrinogen Decarboxylase / Q000037:antagonists & inhibitors; D014578:Uroporphyrins / Q000096:biosynthesis*
D011166:Porphyrins; D014578:Uroporphyrins; D002701:Chloramphenicol; D014575:Uroporphyrinogen Decarboxylase; D004996:Ethidium