Porphyria Caused by Hexachlorobenzene and Other Polyhalogenated Aromatic Hydrocarbons

Uroporphyria development in cultured chick embryo fibroblasts long‐term treated with chloramphenicol and ethidium bromide

“…That mitochondria can be involved in the development of uroporphyria is a possibility that has been evoked by other investigators [2,3,17]. However, no direct correlation has yet been established between the impairment of mitochondrial functions and the generally accepted idea that uroporphyria induced in mammals and birds by xenobiotics is caused by decreased activity of uroporphyrinogen decarboxylase.…”

“…However, no direct correlation has yet been established between the impairment of mitochondrial functions and the generally accepted idea that uroporphyria induced in mammals and birds by xenobiotics is caused by decreased activity of uroporphyrinogen decarboxylase. Speculations on the mechanism of action of these compounds include decreased synthesis and/or increased catabolism of uroporphyrinogen decarboxylase ([18], but see [19]), direct inhibition of the enzyme by binding of the xenobiotics and/or their metaboiites to a group essential for catalytic activity [20], inactivation of the enzyme by formation of oxygen radicals [21] and alterations of the redox state of the ceils leading to decreased ability to maintain uroporphyrinogen and/or the catalytic thiol group of the enzyme in the reduced form (review [2]). Considering the fact that CEF can be cultivated for long periods in the presence of CAP and EtdBr and that the capacity of the cells to decarboxylate uroporphyrinogen can be modulated by CAP, CEF appear to provide a good model system to obtain some insight into these problems.…”

“…Among the xenobiotics tested, polyhalogenated aromatic hydrocarbons (PHA) are known to cause a massive production of uroand heptacarboxyporphyrins in the liver of treated animals (review [2]). This type of porphyria is a time-dependent process which usually takes at least a week in birds [3].…”

“…When the cells are incubated in the presence of caminolevulinate (ALA), the development of uroporphyria is a function of the concentration of xenobiotics and appears over a period of less than 24 h [6,7]. The mechanism whereby PHA induce uroporphyria in birds as well as mammals in vivo and in vitro is still obscure, but the data obtained thus far show that this phenomenon is specifically related to the reduction in activity of uroporphyrinogen decarboxylase [2].…”

Mutants of Saccharomyces cerevisiae Partially Defective in the Last Steps of the Haem Biosynthetic Pathway: Isolation and Genetical Characterization

“…These diseases are characterized by an excessive increase in production and excretion of porphyrin and/or its precursors due to partial deficiencies of a specific enzyme. The profile of accumulated and excreted haem precursors indicates the existence of compensatory mechanisms overcoming the enzymic defect, to maintain nearly normal end-product synthesis (see references in Elder, 1978 ;DOSS, 1982).…”