Skip to main content
SpringerLink
Log in

In Vivo and In Vitro Mixed-Function Oxygenase Activity and Vitellogenin Induction in Fish and in Fish and Rat Liver Cells by Stilbenes Isolated from Scotch Pine (Pinus sylvestris)

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

Many types of pulp and paper mill effluents have the ability to induce mixed-function oxygenase (MFO) activity and vitellogenin (VTG) protein in exposed male fish. The search for the compounds responsible for MFO induction has led to several classes of compounds, among them retene and stilbenes. The objective of this study was to investigate the biological activities of candidate stilbene compounds. Three stilbenes, 3,5-dihydroxystilbene (pinosylvin; P1), 3-hydroxy-5-methoxystilbene (P2), and 3,5-dimethoxystilbene (P3), were extracted from Scotch pine (Pinus sylvestris) and purified to evaluate their ability to induce MFO activity in vitro using ethoxyresorufin-O-deethylase (EROD) activity in a rat hepatoma cell line (H4IIE). As these compounds may be chlorinated during pulp bleaching, chlorination of P2 was undertaken, producing di- and trichlorinated isomers (Cl-P2), which were also tested. Compounds were tested for EROD-inducing ability in vivo by exposing juvenile rainbow tout (Oncorhynchus mykiss) to waterborne concentrations (0.010 to 1.0 mg/L) for 4 days. Compounds were also tested for their ability to induce VTG in trout primary liver cells in vitro. The stilbenes were weak inducers of EROD and VTG. H4IIE EROD was induced by all four compounds, with the most potent induction by P3, followed by P1, the Cl-P2 mixture, and then P2. Induction for all four stilbenes was from 3.13 × 10−3 to 3.57 × 10−4 as potent as retene and about 1.11 × 10−5 to 1.20 × 10−6 as potent as TCDD. Juvenile rainbow trout did not show EROD induction after exposures to P1, P2, or the Cl-P2 mixture, whereas P3 caused activity fourfold above that of controls. P1, P3, and Cl-P2 all weakly induced VTG in rainbow trout hepatocytes. The most potent inducer of VTG was Cl-P2, followed by P3 and P1. The results show the ability of wood-derived stilbenes to cause weak MFO induction in fish and in rat liver cells and to weakly induce vitellogenin in fish liver cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Bachelor FW, Loman AA, Snowdon LR (1970) Synthesis of pinosylvin and related heartwood stilbenes. Can J Chem 48:1554–1557

    Article  CAS  Google Scholar 

  • Belknap AM, Solomon KR, MacLatchy DL, Dube MG, Hewitt LM (2006) Identification of compounds associated with testosterone depressions in fish exposed to bleached kraft pulp and paper mill chemical recovery condensates. Environ Toxicol Chem 25:2322–2333

    Article  CAS  Google Scholar 

  • Burnison BK, Hodson PV, Nuttley DJ, Efler S (1996) A bleached-kraft mill effluent fraction causing induction of a fish mixed-function oxygenase enzyme. Environ Toxicol Chem 15:1524–1531

    Article  CAS  Google Scholar 

  • Burnison K, Comba M, Carey J, Parrott J, Sherry J (1999) Isolation and tentative identification of compounds in bleached kraft mill effluents capable of causing mixed function oxygenase induction in fish. Environ Toxicol Chem 18:2882–2887

    Article  CAS  Google Scholar 

  • Chiron H, Drouet A, Ernst D, Heller W, Sanderman H (1998) cDNA cloning and characterization of two putative pinosylvin O-methyltransferases from Scots pine. Extended abstract. 2nd International Electronic Conference on Synthetic Organic Chemistry, 1–3 September, 1998

  • Fragoso NM, Parrott JL, Hahn ME, Hodson PV (1998) Chronic retene exposure caused sustained induction of CYP1A activity and protein in rainbow trout (Oncorhynchus mykiss). Environ Toxicol Chem 17:2347–2353

    CAS  Google Scholar 

  • Fragoso NM, Hodson PV, Kozin IS, Brown RS, Parrott JL (1999) Kinetics of mixed function oxygenase induction and retene excretion in retene-exposed rainbow trout (Oncorhynchus mykiss). Environ Toxicol Chem 18:2268–2274

    CAS  Google Scholar 

  • Haasch ML, Quardokus EM, Sutherland LA, Goodrich MS, Lech JJ (1993) Hepatic cyp1a1 induction in rainbow trout by continuous flowthrough exposure to beta-naphthoflavone. Fund Appl Toxicol 20:72–82

    Article  CAS  Google Scholar 

  • Hewitt LM, Carey JH, Munkittrick KR, Dixon DG (1996) Examination of bleached kraft mill effluent fractions for potential inducers of mixed function oxygenase activity in rainbow trout. In: Servos MR, Munkittrick KR, Carey JH, Van der Kraak G (eds) Environmental fate and effects of bleached pulp mill effluents. St. Lucie Press, Delray Beach, FL, pp 79–94

    Google Scholar 

  • Hewitt LM, Parrott JL, McMaster ME (2006) A decade of research on the environmental impacts of pulp and paper mill effluents in Canada: sources and characteristics of bioactive substances. J Toxicol Environ Health B 9:341–356

    Article  CAS  Google Scholar 

  • Hodson PV, Efler S, Wilson JY, El-Shaarawi A, Maj M, Williams TG (1996) Measuring the potency of pulp mill effluents for induction of hepatic mixed function oxygenase activity in fish. J Toxicol Environ Health 49:101–128

    Google Scholar 

  • Hudlicky M (1980) An improved apparatus for the laboratory preparation of diazomethane. J Org Chem 45:5377–5378

    Article  CAS  Google Scholar 

  • Kohli J, Comba M, Carey J (2003) Isolation and identification of stilbenes compounds in several pulp wood species. Poster presentation at Seventh International Water Association Symposium on Forest Industry Wastewater, Seattle, WA, 1–4 June, 2003

  • Kovacs T, Martel P, Ricci M, Michaud J, Voss R (2005) Further insights into the potential of pulp and paper mill effluents to affect fish reproduction. J Toxicol Environ Health A 68:1621–1641

    Article  CAS  Google Scholar 

  • Lowell RB, Ribey SC, Ellis IK, Porter EL, Culp JM, Grapentine LC, McMaster ME, Munkittrick KR, Scroggins RP (2003) National assessment of the pulp and paper environmental effects monitoring data. Report No. 03-521. National Water Research Institute, Burlington, ON, Canada

  • Marlatt VL, Hewitt LM, Van Der Kraak G (2006) Utility of in vitro test methods to assess the activity of xenoestrogens. Environ Toxicol Chem 25:3204–3212

    Article  CAS  Google Scholar 

  • Martel PH, Kovacs TG, O’Connor BI, Voss RH (1997) Source and identity of compounds in a thermomechanical pulp mill effluent inducing hepatic mixed-function oxygenase activity in fish. Environ Toxicol Chem 16:2375–2383

    Article  CAS  Google Scholar 

  • Martel P, Kovacs T, Voss R (2004) Survey of pulp and paper mill effluents for their potential to affect fish reproduction. In: Borton DL, Hall TJ, Fisher RP, Thomas JF (eds) Pulp and paper mill effluent environmental fate and effects. DEStech, Lancaster, PA, pp 78–91

    Google Scholar 

  • Osborne N, Sherry JP, Currie S (2007) The role of hsp90 in 17α-ethynylestradiol-induced endocrine disruption in rainbow trout (Oncorhynchus mykiss) hepatocytes. Ecotox Environ Safety 68:13–19

    Article  CAS  Google Scholar 

  • Parrott JL, Burnison BK, Hodson PV, Comba ME, Fox ME (1994) Retene-type compounds – inducers of hepatic mixed function oxygenase (MFO) in rainbow trout (Oncorhynchus mykiss)? Poster presented at 2nd international conference on environmental fate and effects of bleached pulp mill effluents, Vancouver, BC, 6–9 November 1994

  • Parrott JL, McMaster ME, Hewitt LM (2006) A decade of research on the environmental impacts of pulp and paper mill effluents in Canada: development and application of bioassays. J Toxicol Environ Health B 9:297–317

    Article  CAS  Google Scholar 

  • Schreer A, Tinson C, Sherry JP, Schirmer K (2005) Application of Alamar blue/5-carboxyfluorescein diacetate acetoxymethyl ester as a noninvasive cell viability assay in primary hepatocytes from rainbow trout. Anal Biochem 344:76–85

    Article  CAS  Google Scholar 

  • Simmons DB, Trudeau VL, Marlatt VL, Moon TW, Sherry JP, Metcalfe CD (2008) Interaction of stilbene compounds with human and rainbow trout estrogen receptors. Environ Toxicol Chem 27:442–451

    Article  CAS  Google Scholar 

  • Tillitt DE, Giesy JP, Ankley GT (1991) Characterization of the H4IIE rat hepatoma cell bioassay as a tool for assessing toxic potency of planar halogenated hydrocarbons (PHHs) in environmental samples. Environ Sci Technol 25:87–92

    Article  CAS  Google Scholar 

  • Tysklind M, Tillitt D, Eriksson L, Lundgren K, Rappe C (1994) A toxic equivalency factor scale for polychlorinated dibenzofurans. Fund Appl Toxicol 22:277–285

    Article  CAS  Google Scholar 

  • Van der Kraak G, Munkittrick K, McMaster ME, MacLatchy DL (1998) A comparison of bleached kraft mill effluent, 17-estradiol and B-sitosterol effects on reproductive function in fish. In: Kendall RJ, Dickerson RL, Suk WA, Giesy JP (eds) Principles and processes for evaluating endocrine disruption in wildlife. SETAC Press, Pensacola, FL, pp 249–265

    Google Scholar 

Download references

Acknowledgments

The authors thank Tina Hooey, Beverley Blunt, and Mark Baker for technical assistance.

Author information

Authors and Affiliations

  1. Water Science and Technology Directorate, Environment Canada, National Water Research Institute, 867 Lakeshore Road, Burlington, ON, L7R 4A6, Canada

    Joanne L. Parrott, Jagmohan Kohli, James P. Sherry & L. Mark Hewitt

Authors
  1. Joanne L. Parrott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jagmohan Kohli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James P. Sherry
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Mark Hewitt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joanne L. Parrott.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parrott, J.L., Kohli, J., Sherry, J.P. et al. In Vivo and In Vitro Mixed-Function Oxygenase Activity and Vitellogenin Induction in Fish and in Fish and Rat Liver Cells by Stilbenes Isolated from Scotch Pine (Pinus sylvestris). Arch Environ Contam Toxicol 60, 116–123 (2011). https://doi.org/10.1007/s00244-010-9539-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00244-010-9539-9

Keywords

Search

Navigation