[en] Polychlorinated biphenyls (PCBs) are widespread residual micropollutants which accumulate in living organisms, probably as a consequence of their high lipophilicity. Cultured foetal rat hepatocytes used as target cells constitute an interesting in vitro model for studying the mechanisms of action of PCBs. In this paper, and the accompanying one (Toxicology 98 (1995) 83-94), we have used this model to investigate the effects of PCBs on several cellular parameters. The inducibility of CYPIA1 is the most sensitive parameter studied, as shown by the induction of ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase activities at PCB concentrations as low as 1 microM. Dexamethasone treatment of the cells potentiates this induction. PCB induction is reversible and occurs even in cells cultured for several days. CYP2B and CYP3A seem unaffected by PCBs in this experimental system. By inducing CYP1A1, PCBs can trigger the 'activation' of xenobiotics, such as polycyclic hydrocarbons, into mutagenic compounds.
Effects of Pcbs (Aroclor 1254) on Cytochrome-P450 Expression and Monooxygenase Activities in Cultured Foetal Rat Hepatocytes
Publication date :
12 April 1995
Journal title :
Toxicology
ISSN :
0300-483X
eISSN :
1879-3185
Publisher :
Elsevier, Netherlands
Volume :
98
Issue :
1-3
Pages :
95-103
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
BELSPO - Service Public Fédéral de Programmation Politique scientifique F.R.S.-FNRS - Fonds de la Recherche Scientifique
Funding text :
Grant from the Service de la Programmation de la Politique Scientitique (HI-I/46 Health Hazards Impulse Programme); Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS (FRSM: convention no. 3.9006.90)
Ames, Durston, Yamasaki, Lee (1973) Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc. Natl. Acad. Sci. USA 70:2281.
Bollinne, Kremers, Kolodjici, Gielen (1987) Long-term maintenance of monooxygenase activities in cultured foetal rat hepatocytes. Cell Differ. 21:239.
Donato, Gomez-Lechon, Castell (1990) Effects of xenobiotics on monooxygenase activities in cultured human hepatocytes. Biochem. Pharmacol. 39:1321.
Ferrari, Kremers, Batt, Gielen, Siest (1992) Differential effects of human recombinant interleukin-1β on cytochrome P-450-dependent activities in cultured foetal rat hepatocytes. Drug Metab. Dispos. 20:407.
Flodström, Hemming, Wärngård, Ahlborg (1990) Promotion of altered hepatic foci development in rat liver, cytochrome P450enzyme induction and inhibition of cell-cell communication by DDT and some structurally related organohalogen pesticides. Carcinogenesis 11:1413.
Gomez-lechon, Donato, Ponsoda, Jover, Castell (1992) Experimental in vitro models to evaluate hepatotoxicity. In Vitro Alternatives to Animal Pharmacotoxicology , J.V. Castell, M.J. Gomez-Lechon, Farmaindustria, seri Cientifica, Madrid; 85.
Hutzinger, Safe, Zitko The Chemistry of PCBs, CRC Press, Boca Raton, FL; 1974.
Jaiswal, Haaparanta, Luc, Schembri, Adesnik (1990) Glucocorticoid regulation of a phenobarbital-inducible cytochrome P-450 gene: The presence of a functional glucocorticoid response element in the 5′-flanking region of the CYP2B2 gene. Nucleic Acids Res. 18:4237.
Kimbrough (1987) Human health effects of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs). Ann. Rev. Pharmacol. Toxicol. 27:87.
Kremers (1986) Drug metabolism in cultured foetal hepatocytes. Research in Isolated and Cultured Hepatocytes J , A. Guillouzo, C. Guguen-Guillouzo, LibbeyInserm, London, Paris; 285.
Kremers, Laemmli (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680.
Letawe-Goujon, Kremers, Beaune, Paye, Gielen (1984) Preparation and characterization of monoclonal antibodies against phenobarbital-inducible cytochrome P-450. Biochem. Biophys. Res. Commun. 119:744.
Lowry, Rosebrough, Farr, Randall (1951) Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265.
McMillan, Shaddock, Casciano, Arlotto, Leakey (1991) Differential stability of drug-metabolizing enzyme activities in primary rat hepatocytes, cultured in the absence or presence of dexamethasone. Mutat. Res. 249:81.
Nagaoka, Kamuro, Oda, Yoshida (1991) Effects of polychlorinated biphenyls on cholesterol and ascorbic acid metabolism in primary cultured rat hepatocytes. Biochem. Pharmacol. 41:1259.
Ong, Mukhtar, Wolf, Leiger (1980) Differential effects of cytochrome P-450 inducers and promutagen activation capabilities and enzymatic activities of S9 from rat liver. J. Environ. Pathol. Toxicol. 4:55.
Paine (1990) The maintenance of cytochrome P450 in rat hepatocyte cultures: some applications of liver cell cultures to the study of drug metabolism, toxicity and the induction of the cytochrome P450 system. Chem.-Biol. Interact. 74:1.
Paye, Beaune, Kremers (1984) Quantification of two cytochrome P-450 isozymes by an enzyme-linked immunoabsorbent assay (ELISA). Biochem. Biophys. Res. Commun. 122:137.
Safe (1984) Polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs), biochemistry, toxicology and mechanisms of action. CRC Crit. Rev. Toxicol. 13:319.
Sherratt, Banet, Prough (1990) Glucocorticoid regulation of polycyclic aromatic hydrocarbon induction of cytochrome P450IA1, glutathione S-transferases, and NAD(P)H:quinone oxidoreductase in cultured foetal rat hepatocytes. Mol. Pharmacol. 37:198.
Sinclair, Bement, Lambrecht, Gorman, Sinclair (1990) Chlorinated biphenyls induce cytochrome P450IA2 and uroporphyrine accumulation in cultures of mouse hepatocytes. Arch. Biochem. Biophys. 281:225.
Thomé, Roelandt, Goffinet, Stouvenakers, Kremers (1994) Cytotoxic effects of Aroclor 1254 on ultrastructure and biochemical parameters in cultured foetal rat hepatocytes. Toxicology 98:83-94.
Towbin, Staehelin, Gordon (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA 76:4350.
Van Cantfort, Goujon-Letawe, Gielen (1979) Benzo[a]pyrene metabolism in rat foetal hepatocytes in culture. Improved methodology and effect of substrate concentration. Chem.-Biol. Interact. 28:147.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.
