Chem.-Biol. Interactions, 41 (1982) 131--139 131 Elsevier Scientific Publishers Ireland Ltd. STRUCTURE-ACTIVITY RELATIONSHIPS OF CHLORINATED BENZENES AS INDUCERS OF DIFFERENT FORMS OF CYTOCHROME P-450 IN RAT LIVER J.A. GOLDSTEIN*, P. LINKO, J.N. HUCKINS a and D.L. STALLING a National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, ArC 27709 and aUnited States Department of the Interior, Fish and Wildlife Service, Columbia National Fishery Research Laboratory, Columbia, MO 65201 (U.S.A.) (Received November 7th, 1981) (Revision received March 10th, 1982) (Accepted March 13th, 1982) SUMMARY Hexachlorobenzene (HCB) produced increases in ethoxyresorufin (ERR) O-deethylase, aryl hydrocarbon hydroxylase (AHH) and aminopyrine N- demethylase activities in rat liver microsomes which were intermediate between those produced by phenobarbital and 3,4-benzpyrene (BP). a- Naphthoflavone (ANF) selectively 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 (M r = 56 000). How- ever, 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 pro- duced by HCB. In contrast to HCB, all other chlorinated benzenes tested resembled phenobarbital as inducers. INTRODUCTION Cytochrome P-450 is the terminal oxidase of the mixed-function oxidase system which metabolizes numerous xenobiotics and some endogenous com- pounds. There is considerable evidence for multiple forms of this hemo- Abbreviations: AHH, aryl hydrocarbon hydroxylase; ANF, ~-naphthoflavone; BP, 3,4- benzpyrene; ERR, ethoxyresorufin; ETNC, ethyl isocyanide; HCB, hexachlorobenzene; 3-MC, 3-methylcholanthrene; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; TCDD, tetrachlorodibenzo-p-dioxin.