Biochmhl Pb~~i~, Vol. 26, pp. 1501-1505. perSamon Press, 1977. Printed in Great Britain. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR INDUCTION zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA OF ARYL HYDROCARBON (BENZO[a]PYRENE) HYDROXYLASE AND 2-ACETYLAMINOFLUORENE N-HYDROXYLASE BY POLYCYCLIC HYDROCARBONS IN REGENERATING LIVER FROM INBRED STRA INS OF MICE* ALAN R. BGGBIs, CHARLES REINHOLD and SNOEEI S. THoRGErRssGNj’ Section on Molecular Toxicology, Developmental Pharmacology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20014, U.S.A. (Received 23 October 1976; accepted 29 December 1976) Abstract-The effect of partial hepatectomy (67-75 per cent excised) on aryl hydrocarbon (benzo[aJpyr- ene) hydroxylase and 2-acetylaminofluorene N-hydroxylase activities in genetically responsive C57BL/6N and nonresponsive DBA/2N inbred strains of mice was studied. Basal aryl hydrocarbon hydroxylase activity in C57BL/6N mice is reduced by 70 per cent within 12 hr but returns to control vahres between 36 and 48 hr after the operation and remains at that level thereafter. Similar, but less pronounced, changes are observed in the DBA/2N mouse. Treatment with 3-methylcholanthrene (80 mg kg-’ intraperitoneally) 1 hr after partial hepatectomy induces aryl hydrocarbon hydroxylase in C57BL/6N mice, by 48 hr, to the same extent as in mice with intact livers. In DBA/2N mice, even after partial hepatectomy, treatment with 3-methylcholanthrene has no effect on aryl hydrocarbon hydroxylase activity. The etfect of partial hepatectomy and 3-methylchol~threne treatment on t-acetyl- aminoffuorene N-hydroxylase activity in both strains of mice is similar to that observed on aryl hydro- carbon hydroxylase activity. The aryl hydrocarbon hydroxylaae in the liver of C57BL/6N mice is induced by 3-methylcholanthrene treatment, whereas this enzyme is not induced by 3-methylcholanthrene in the liver of DBA/2N mice. Although genetic differences in aryl hydrocarbon hy- droxylase induction exist in cell culture from fetal mouse liver, cells from a strain normally nonrespon- sive to polycyclic hydrocarbons do exhibit some in- duction of aryl hydrocarbon hydroxylase activity [l J. Regenerating liver is similar to cell culture in that DNA is rapidly replicating and the hepatocytes are less differentiated. Thus, it is possible after partial hepatectomy that aryl hydrocarbon hydroxylase might become partially or completely inducible by polycyclic hydrocarbons in the liver of nonresponsive mice. This paper presents evidence that partial hepa- tectomy neither a@ects the max~um 3-methyi~hol- anthrene-induced activities of aryl hydrocarbon hy- droxylase and Zacetylaminotluorene N-hydroxylase in the responsive C57BL/6N mice nor causes an in- crease in these enzyme activities after 3-methylcho- lanthrene treatment in the nonresponsive DBA/2N mice. *A portion of this work [A. R. Boobis, C. Reinhold and S. S. Thorgeirsson, P~~~o~~~s 17,249 (197511was presented at the Fall Meeting of-American &cieti for Pharmacology and Experimental Therapeutics. Davis. CA. August, 1975: - _ t To whom reprint requests should be addressed. Pres- ent address: Laboratory of Chemical Ph~a~~~, Building 37, Room 5C-30, National Cancer Institute, National Institutes of Health, Bethesda, MD 20014. MATERIALS AND METHODS The poiycyclic hydrocarbons benzo[a]pyrene and 3-methylcholanthrene were purchased from Sigma Chemiottl Co. (St. Louis, MO) and J. T. Baker Chemi- cal Co. (Phillipsburg, NJ), respectively; fi-naphthofla- vone was purchased from Aldrich Chemical Co. (Mil- waukee, WI); Z-a~tyl~inofluorene from Eastman Kodak Co. (Rochester, NY); and NADPH and NADH from Sigma Chemical Co. [9-r4C]-2-acetyl- atninofluorene (10.5 mCi/m-mole), purchased from New England Nuclear {Boston, MA), was shown to be more than 99.9 per cent pure by thin-layer chromatography (chloroform-methanol, 97:3, v/v). Authentic N-hydroxy-2-acetylaminofluorene was generously given to us by Dr. Elizabeth Weisburger, National Cancer Institute. All other reagents were of the best commercial grade available. The inbred C57BL/6N and DBA/2N mice used in these studies were obtained from the National Institutes of Health Animal Supply. Tre~e~t o~a~~~s. The mice were kept on stan- dard hardwood bedding in plastic cages and fed Wayne Lab-Blox chow ad lib. The environment in the animal room was controlled as previously de- scribed [2]. Mice of either sex [3], between 4 and 6 weeks of age at the time of operation, were used. For studies involving enzyme induction by the aromatic hydrocarbons 3-methylcholanthrene or fl-naphthofla- vone, 80mg of the compound/kg of body weight, in corn oil, was administered ~tra~riton~ly to each mouse at various time intervals before sacrifice; con- trols received an equivalent volume of corn oil alone.