Summary
Pathways of biotransformation of the carcinogenic polycyclic hydrocarbon fluoranthene in individual isolated perifused liver cells were delineated using noninvasive microfluorescence spectroscopic techniques. An example of heterogeneity of coupling between phase I and phase II enzymes detected in a population of β-naphthoflavone-induced rat liver cells demonstrates the usefulness of the experimental model of perifused liver cells.
Similar content being viewed by others
References
Babson JR, Russo-Rodriguez SE, Wattley RV, Bergstein PL, Rastetter WH, Liber HL, Andon BM, Thilly WG, Wogan GN (1986) Microsomal activation of fluoranthene to mutagenic metabolites. Toxicol Appl Pharmacol 85:355–366
Busby WF, Goldman WE, Newborne PM, Wogan GN (1984) Tumorigenicity of fluoranthene in a new born mouse bioassay. Carcinogenesis 5:1311–1316
Conway JG, Kauffman FC, Tsukada T, Thurman RG (1984) Glucuronidation of 7-hydroxycoumarin in periportal and pericentral regions of the liver lobule. Mol Pharmacol 25:487–493
El Mouelhi M, Kauffman FC (1986) Sublobular distribution of transferase and hydrolases associated with glucuronide, sulfate and glutathione conjugation in human liver. Hepatology 6:450–456
Foster JR, Elcombe CR, Boobis AR, Davies DS, Sesardic D, McQuade J, Robson RT, Hayward C, Lock EA (1986) Immunocytochemical localization of cytochrome P-450 in hepatic and extra-hepatic tissues of the rat with a monoclonal antibody againts cytochrome P-450. Biochem Pharmacol 35:4543–4554
Gooding PE, Chayen J, Sawyer B, Slater TF (1978) Cytochrome P-450 distribution in rat liver and the effect of sodium phenobarbitone administration. Chem Biol Interact 20:299–310
Höhne M (1983) Biotransformation des Fluoranthen durch das Cytochrom P-450-System und Charaketerisierung von rekonstituierten Cytochrom P-450-Systemen. Dissertation, Freie Universität Berlin
Ivanetich KM, Ziman MR, Bradshaw JJ (1982) 1,1,1-Trichloropropene-2,3-oxide: an alternate mechanism for its inhibition of cytochrome P-450. Res Commun Chem Pathol Pharmacol 35:111–120
Jungermann K, Katz N (1982) Metabolic heterogeneity of liver parenchyma. In: Sies H (ed) Metabolic compartmentation. Academic Press, London New York Paris, pp 411–435
LaVoie EJ, Hecht SS, Bedenko V, Hoffmann D (1982) Identification of the mutagenic metabolites of fluoranthene, 2-methylfluoranthene and 3-methylfluoranthene. Carcinogenesis 3:841–846
Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. J Biol Chem 239:2379–2385
Rastetter WH, Nachbar RB, Russo-Rodriguez S, Wattley RV (1982) Fluoranthene: synthesis and mutagenicity of four diol epoxides. J Org Chem 47:4873–4878
Rice JE, LaVoie EJ, Hoffmann D (1982) synthesis of the isomeric phenols and the trans-2,3-dihydrodiol of fluoranthene. J Org Chem 48:2360–2363
Schlenker A (1982) Untersuchung der Biotransformation von Fluoranthen in Mikrosomen, Leberzellsuspensionen und einzelnen Leberzellen. Dissertation, Technische Universität Braunschweig
Seglen PO (1973) Preparation of rat liver cells. Exp Cell Res 76:25–30
Shenbor MI, Cheban GA (1969) Preparation of fluoranthenol-3 by the action of lead tetraacetate on fluoranthene. J Org Chem USSR 5:143
Shimada T, Sato R (1979) Inhibition of mono-oxygenase activities by 1,1,1-trichloropropene 2,3-oxide, an inhibitor of epoxide hydrase, in rat liver microsomes. Biochem Pharmacol 28:1777–1781
Stier Am, Nolte KH, Schlenker A, Schumann W, Zuretti FM (1980) Toxicological studies of liver cells by microspectrofluorometry. Arch Toxicol 44:45–54
Stier A, Finch SAE, Greinert R, Taniguchi H (1985) Membrane protein interactions in biotransformation. In: Vereczkey L, Magyar K (eds) Cytochrome P-450, biochemistry, biophysics and induction. Akademiai Kiado, Budapest, pp 139–146
Strobel HW, Lau PP (1982) Five forms of cytochromes P-450 from β-naphthoflavone pretreated rats. In: Sato R, Kato R (eds) Microsomes, drug oxidations, and drug toxicity. Wiley, New York, pp 91–92
Ullrich D, Fischer G, Katz N, Bock KW (1984) Intralobular distribution of UDP-glucuronosyltransferase in livers from untreated, 3-methylcholanthrene- and phenobarbital-treated rats. Chem Biol Interact 48:181–190
Wolf CR, Buchmann A, Friedberg T, Moll E, Kuhlmann WD, Kunz HW, Oesch F (1984) Dynamics of the localization of drug metabolizing enzymes in tissues and cells. Biochem Soc Trans 12:60–62
Author information
Authors and Affiliations
Additional information
Dedicated to Werner Kunz on the occasion of his 65th birthday
Rights and permissions
About this article
Cite this article
Stier, A., Schlenker, A., Sidhu, J. et al. Heterogeneity of biotransformation of fluoranthene in perifused liver cells. J Cancer Res Clin Oncol 114, 39–46 (1988). https://doi.org/10.1007/BF00390484
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00390484