Supporting information

BFCOD ACTIVITY IN FISH CELL LINES AND ZEBRAFISH EMBRYOS AND ITS MODULATION BY CHEMICAL LIGANDS OF HUMAN ARYL HYDROCARBON AND NUCLEAR RECEPTORS

N. Creusot1*, F. Brion1, B. Piccini1, H.Budzinski2, J.M. Porcher1 and S. Aït-Aïssa1*

1INERIS, Unité Écotoxicologie in vitro et in vivo, Parc ALATTA, BP2,f-60550 Verneuil-en-Halatte, France

2EPOC/ LPTC – UMR 5805 CNRS Université Bordeaux 1, f-33405 Talence, France

*Corresponding authors:

Tel +33 344 556511, Fax +33344556767, E-mail: ;

Table S1. Examples from the literature on chemical compounds differently active on CYP1A and CYP3A enzymes in mammals and fish; in terms of substrate, induction and inhibition of the enzymatic activity. The mechanisms responsible for modulation may be either at the transcriptional level (e.g. through nuclear receptor activation) or by direct inhibition on the enzyme (e.g. suicide substrate).

Enzymes / Substrates / Inducers / Inhibitors
Mammals / CYP1A / estradiolo, estroneo / caffeinb, theophyllinb, flutamideb, lidocaineb, PAHs (BaP, 3-MC, BNF), Dioxins, Furans, PCBs (77, 126, 169), Rifampicind, Fenvalerated / α-naphtoflavoneb, fyrafyllineb, ketoconazolem, clotrimazolem, elliptiscinen
CYP3A / midazolamb, felopidineb, erythromycinb, nifepidineb, triazolamb, simvastatinb, cyclosporine Ab, quinidineb, vincristineb, testosteroneb, progesteroneb, œstradiolb, androstenedioneb, bile acidb / testosteronem, alprazolam, lovastatinb, dexamethasoned, h, phenobarbitald, rifampicind, g, clotrimazole, α-naphtoflavonem, progesteronem, tamoxifeni, prednisolone, omeprazolei, Phtalateh, chlorpyriphosd, fenvalerated / ketoconazolem, Clotrimazolem, itraconazoleb, clarythromycinb, gestodenb, ritonavirb, verapamilb, ethinyl-estradiolm, tamoxifenm, carbamazepinm, erythromycinm
Fish / CYP1A / estradiolc, BaPc, 7-ethoxyresorufinc, phenacetinc / PAHsc, Dioxinsc, Furansc, PCBsc , fluoxetinep, carbamazepinp, fenofibratep, clotrimazolef / elliptiscinea, cadmium, TBT, α-naphtoflavonea, parathiona, clotrimazolea,e, ketoconazolea, j, miconazolea, isosafrolea, 2-aminoanthracene c, fluoranthenc, α-naphtoflavone c, PCB77c, ethinyl-estradiolj
CYP3A / testosteronec, progesteronec, estradiolc, BaPc, nifepidinec, ethoxycoumarinc, benzyloxy-4-[trifluoromethyl]-coumarinc / rifampicing,l, estrogensc,
α-naphtoflavonec / α-naphtoflavonea, parathiona, clotrimazolea,e, ketoconazolea, j,k, miconazolea, nonylphenolj, isosafrolea, piperonyl butoxydea, gestodenea, 17-α-ethinyl-estradiola, 1-amino-benzotriazolea; elliptiscinea

From a, Miranda et al. 1998 (CYP1A1 and CYP3A27 in rainbow trout);b, Pelkonen et al. 2008 (CYP1A2 and CYP3A4/5 in humans);c, Schlenk et al. 2008 (Fish); d, Abass et al. 2012 (CYP1A2 and CYP3A4 in human); e, Burkina et al. 2013(rainbow trout hepatocytes); f, Navas et al. 2004 (rainbow trout hepatocytes); g, Christen et al. 2009 (human and fish cell lines); h, Cooper et al. 2008(human and rat hepatic cell lines); i, Cui et al. 2008; j, Hasselberg et al. 2005(atlantic cod in vivo); k, Hegelund et al. 2004(rainbow trout and Killifish); l, Li et al. 2008 (Grass carp); m, Stresser et al. 2000 (human); n, Aimova 2005; o, Sanderson &van den Berg 2003; p, Laville et al. 2004 (rainbow trout hepatocytes)

Abass K, Lämsä V, Reponen P, Küblbeck J, Honkakoski P, Mattila S, Pelkonen O, Hakkola J (2012): Characterization of human cytochrome P450 induction by pesticides. Toxicology

Aimova (2005): ANTITUMOR DRUG ELLIPTICINE INHIBITS THE ACTIVITIES OF RAT HEPATIC CYTOCHROMES P450.

Burkina V, Zlabek V, Zamaratskaia G (2013): Clotrimazole, but not dexamethasone, is a potent in vitro inhibitor of cytochrome P450 isoforms CYP1A and CYP3A in rainbow trout. Chemosphere

Christen V, Oggier DM, Fent K (2009): A Microtiter-Plate-Based Cytochrome P450 3a Activity Assay in Fish Cell Lines. Environ. Toxicol. Chem. 28, 2632-2638

Cooper BW, Cho TM, Thompson PM, Wallace AD (2008): Phthalate induction of CYP3A4 is dependent on glucocorticoid regulation of PXR expression. Toxicol. Sci. 103, 268-277

Cui XM, Thomas A, Gerlach V, White RE, Morrison RA, Cheng KC (2008): Application and interpretation of hPXR screening data: Validation of reporter signal requirements for prediction of clinically relevant CYP3A4 inducers. Biochem. Pharmacol. 76, 680-689

Hasselberg L, Grøsvik BE, Goksøyr A, Celander MC (2005): Interactions between xenoestrogens and ketoconazole on hepatic CYP1A and CYP3A, in juvenile Atlantic cod (Gadus morhua). Comparative Hepatology 4

Hegelund T, Ottosson K, Radinger M, Tomberg P, Celander MC (2004): Effects of the antifungal imidazole ketoconazole on CYPIA and CYP3A in rainbow trout and killifish. Environ. Toxicol. Chem. 23, 1326-1334

Laville N, Ait-Aissa S, Gomez E, Casellas C, Porcher JM (2004): Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes. Toxicology 196, 41-55

Li D, Yang XL, Zhang SJ, Lin M, Yu WJ, Hu K (2008): Effects of mammalian CYP3A inducers on CYP3A-related enzyme activities in grass carp (Ctenopharyngodon idellus): Possible implications for the establishment of a fish CYP3A induction model. Comp. Biochem. Physiol. C-Toxicol. Pharmacol. 147, 17-29

Miranda CL, Henderson MC, Buhler DR (1998): Evaluation of chemicals as inhibitors of trout cytochrome P450s. Toxicol. Appl. Pharmacol. 148, 237-244

Navas JM, Chana A, Herradón B, Segner H (2004): Induction of cytochrome P4501A (CYP1A) by clotrimazole, a non-planar aromatic compound. Computational studies on structural features of clotrimazole and related imidazole derivatives. Life Sciences 76, 699-714

Pelkonen O, Turpeinen M, Hakkola J, Honkakoski P, Hukkanen J, Raunio H (2008): Inhibition and induction of human cytochrome P450 enzymes: current status. Archives of Toxicology 82, 667-715

Sanderson T, van den Berg M (2003): Interactions of xenobiotics with the steroid hormone biosynthesis pathway. Pure Appl. Chem. 75, 1957-1971

Schlenk D, Celander M, Gallagher EP, George S, James M, Kullman SW, van den Hurk P, Willett K (2008): Biotansformation in Fishes. In: Di Giulio RT , Hinton DE (Editors), The toxicology of fishes CRC Press - Taylor & Francis Group, pp. 153-234

Stresser DM, Blanchard AP, Turner SD, Erve JCL, Dandeneau AA, Miller VP, Crespi CL (2000): Substrate-dependent modulation of CYP3A4 catalytic activity: Analysis of 27 test compounds with four fluorometric substrates. Drug Metab. Dispos. 28, 1440-1448