Characterization of sheep seminal vesicle cells-a new tool for studying genotoxic effects in vitro.
Recently, primary cultures consisting mostly of fibroblasts and up to 8% epithelial cells have been derived from ram seminal vesicles (SEMV), which contain high levels of prostaglandin H synthase (PHS). PHS-peroxidase can catalyse the metabolic activation of several xenobiotics, for example diethylstilboestrol (DES). Thus SEMV cells can be a useful tool for investigating whether PHS has a role in mediating the adverse genotoxic effects of such substances, provided that a suitable endpoint for genotoxicity can be determined in this model system. Here we report that DES can induce micronuclei at concentrations that are not cytotoxic for the cells. The frequency of micronucleated cells was increased almost three-fold above control values 12 hr post-treatment with 10 mum-DES, and nearly four-fold 24 hr post-treatment with 0.5 mum-4-nitroquinoline oxide. DES induction of micronuclei in SEMV cells is clearly inhibited by addition of indomethacin, a well-known PHS-cyclooxygenase inhibitor. SEMV cells have been further characterized with respect to their hormone receptor content and drug metabolizing capability. Low levels of glucocorticoid receptor were detectable, but neither oestrogen nor progesterone receptors. DES has been shown to be oxidized by PHS-peroxidase in the absence of detectable monooxygenase activity. These data, together with the indomethacin inhibition of micronucleus formation, imply that metabolic activation by PHS is involved in mediating the genotoxic effect of DES.
Foth
J
J
Institute of Toxicology, University of Würzburg, Versbacher Strasse 9, Würzburg, Germany.
Schnitzler
R
R
Jager
M
M
Koob
M
M
Metzler
M
M
Degen
G H
GH