Hexachlorobenzene-induced porphyria in Japanese quail: an in vitro study of changes in cytochrome P-450 and monooxygenases.
The ability of hexachlorobenzene (HCB) to cause changes in the isozymic composition of hepatic monooxygenases of Japanese quail was assessed. HCB-induced changes in the relative concentrations of benzo[a]pyrene metabolites produced in vitro were apparent. HCB treatment also resulted in changes in the responsiveness of ethoxycoumarin O-deethylase (ECOD) and ethoxyresorufin O-deethylase (EROD) to the in vitro cytochrome P-450 inhibitors metyrapone, SKF-525A, and alpha-naphthoflavone. These changes may be indicative of alterations in the major cytochrome P-450 isozymes present following HCB treatment. Of these changes, only an increased responsiveness of ECOD to SKF-525A correlated with the onset of porphyria. The response of Japanese quail to the porphyrogenic action of HCB is more rapid than that found with more commonly used mammalian models. This rapid response is probably due either to the ability of quail to produce greater amounts of porphyrogenic metabolites of HCB than mammals or to a greater sensitivity of the heme pathway in quail to metabolites produced. In either case, this rapid response makes Japanese quail a good model for studying the biochemical mechanism for HCB-induced porphyria. The work presented here extends previous in vivo studies by using in vitro techniques to address the possibility that changes in the proportions of the major cytochrome P-450 isozymes occur in response to HCB and these changes, rather than changes in the total concentration of cytochrome P-450, are important to the development of porphyria.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D002722:Chlorobenzenes; D003370:Coturnix; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006581:Hexachlorobenzene; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism*; D011164:Porphyrias / Q000139:chemically induced* / Q000201:enzymology; D011335:Proadifen / Q000494:pharmacology
D001571:Benzoflavones; D002722:Chlorobenzenes; D006581:Hexachlorobenzene; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1; D008797:Metyrapone