Archives of Toxicology

, Volume 65, Issue 4, pp 344–347 | Cite as

Prostaglandin H synthase dependent metabolism of diethylstilbestrol by ram seminal vesicle cell cultures

  • J. Foth
  • G. H. Degen
Short Communication

Abstract

Prostaglandin H synthase (PHS) peroxidase dependent metabolic activation has been suggested to play a role in mediating adverse effects of various carcinogens. Recently, we derived a cell line from ram seminal vesicles (SEMV cells) to conduct studies on the PHS-mediated metabolism of estrogens and xenobiotics in intact cells with the goal of relating this to an endpoint for genotoxicity inducible in this in vitro model. The present paper describes the drug-metabolizing capability of SEMV cells which has been investigated using radiolabeled diethylstilbestrol (DES) and analysing culture extracts by means of reverse phase HPLC with on-line radioactivity detection and after enzymatic hydrolysis of conjugate fractions. The synthetic estrogen DES is converted to sulfate conjugates and to the oxidative metabolite Z,Z-dienestrol (Z,Z-DIES) in a time-dependent manner. Compounds expected to modulate PHS-dependent co-oxidation of DES increased (arachidonic acid) or inhibited (indomethacin) Z,Z-DIES formation of SEMV cells in culture. A comparison of rates of arachidonic acid turnover to prostaglandins on the one hand and DES oxidation on the other reveals that DES is oxidized despite the presence of competing endogenous cosubstrates of PHS peroxidase. The results clearly indicate that SEMV cells catalyze PHS-dependent oxidation of DES as well as carrying out phase II metabolism in the absence of detectable monooxygenase activity. These features and recent data showing that DES can induce micronuclei in SEMV cells makes them an attractive model for further investigations of the role of PHS in mediating the genotoxicity of DES and other xenobiotics.

Key words

Prostaglandin H synthase Cooxidation Diethylstilbestrol Metabolism SEMV cells 

Abbreviations

ARA

arachidonic acid

DES

diethylstilbestrol

Z,Z-DIES

Z,Z-dienestrol

Indo

indomethacin

MFO

mixed function oxidase

PG

prostaglandin

PHS

prostaglandin-H-synthase

SEMV

seminal vesicles from ram

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • J. Foth
    • 1
  • G. H. Degen
    • 1
  1. 1.Institute of Toxicology, SFB 172University of WuerzburgWuerzburgFRG

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