Drug metabolizing enzyme activities in porcine urinary bladder epithelial cell cultures (PUBEC)
| Autor: | Gisela H. Degen, Ulrike S. Schuhmacher, Christine Guhe, Franz Kiefer, Wolfram Föllmann |
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| Rok vydání: | 1996 |
| Předmět: |
Arylamine N-Acetyltransferase
Swine Health Toxicology and Mutagenesis Urinary Bladder Biology Toxicology Epithelium chemistry.chemical_compound Sulfation Cytochrome P-450 Enzyme System medicine Animals Glucuronosyltransferase Prostaglandin E2 Biotransformation Cells Cultured Carcinogen Glutathione Transferase Urinary bladder General Medicine Glutathione Molecular biology In vitro medicine.anatomical_structure Biochemistry Mechanism of action chemistry Prostaglandin-Endoperoxide Synthases medicine.symptom Drug metabolism medicine.drug |
| Zdroj: | Archives of Toxicology. 70:599-606 |
| ISSN: | 1432-0738 0340-5761 |
| DOI: | 10.1007/s002040050318 |
| Popis: | Drug metabolizing enzyme activities have been determined in cultured porcine urinary bladder epithelial cells (PUBEC) in order to evaluate this system as an in vitro model for studies of urinary bladder carcinogens. Activities of several phase I and II enzymes were measured in cells cultured for various periods and compared with the activities determined in freshly isolated PUBEC. Prostaglandin H synthase mediated production of prostaglandin E2 was found both in freshly isolated and in cultured PUBEC, whereas cytochrome P450 1A1-associated EROD activity was only detectable in freshly isolated bladder cells. The latter activity was not inducible by benz(a)anthracene or 3-methylcholanthrene in PUBEC cultures. N-acetyltransferase (NAT) activity measured with p-aminobenzoic acid, a diagnostic substrate for human NAT-1, was stable and even higher during the culture period compared to freshly isolated cells. In contrast, isoniazid (a substrate for NAT-2) was not acetylated either in fresh or cultured PUBEC. Glutathione S-transferases activity determined with 1-chloro-2,4-dinitrobenzene decreased gradually to 50% after 1 week and to 20% after 4 weeks in culture compared to fresh cells. A similar decline was also observed for UDP-glucuronyltransferase activities measured with 1-naphthol. In accordance with the reported lack of sulfotransferases in pigs, no sulfation of 1-naphthol or 2-naphthylamine was detected in PUBEC. Our results show that cultured porcine urinary bladder epithelial cells maintain several enzyme activities required for the biotransformation of xenobiotics. In future investigations on the mechanism of action of bladder carcinogens PUBEC cultures may thus provide a useful in vitro model for this target tissue. |
| Databáze: | OpenAIRE |
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