Structure-activity relationships of chlorinated benzenes as inducers of different forms of cytochrome P-450 in rat liver.
Hexachlorobenzene (HCB) produced increases in ethoxyresorufin (ERR) O-deethylase, aryl hydrocarbon hydroxylase (AHH) and aminopyrine N-demethylase activities in rat liver phenobarbital which were intermediate between those produced by phenobarbital and 3,4-benzpyrene (BP), alpha-Naphthoflavone (ANF) selectivity inhibited ERR activity in BP and HCB-induced microsomes (94% and 88%). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of liver microsomes indicated that HCB did not produce a detectable increase in a polypeptide with electrophoretic properties similar to those of purified cytochrome P-448 (Mr = 56,000). However, HCB did induce a polypeptide with Mr = 53,000 corresponding to one of two polypeptide bands induced by BP. This polypeptide may represent a second form of cytochrome P-448. Purification of HCB to remove possible dibenzo-p-dioxin impurities did not alter the 'mixed-type' induction produced by HCB. In contrast to HCB, all other chlorinated benzenes tested resembled phenobarbital as inducers.
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001564:Benzo(a)pyrene; D001571:Benzoflavones / Q000494:pharmacology; D001580:Benzopyrenes / Q000494:pharmacology; D002722:Chlorobenzenes / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003580:Cytochromes / Q000096:biosynthesis; D004790:Enzyme Induction; D005260:Female; D006581:Hexachlorobenzene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D001571:Benzoflavones; D001580:Benzopyrenes; D002722:Chlorobenzenes; D003580:Cytochromes; D001564:Benzo(a)pyrene; D006581:Hexachlorobenzene; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; C017170:Cyp1a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D000633:Aminopyrine N-Demethylase; D010634:Phenobarbital