Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver cell aggregates were established from freshly isolated adult rat hepatocytes and non-parenchymal liver cells (NPC) in rotating cultures. One-third of the inoculated cells formed spheroidal aggregates and one-third of the aggregates remained in culture for up to 12 days, expressing a high intracellular lactate dehydrogenase (LDH) activity and ATP content. The 7-ethoxyresorufin O-deethylase (EROD) activity was doubled on day 8 compared with that in freshly isolated cells, and the glutathione S-transferase (GST) activity was preserved to initial level at day 12. Cytochrome P-450 (CYP) isoforms were differentially affected: at day 8, CYP1A1/2 and CYP2B1/2 contents were close to freshly isolated cell contents; CYP3A1/2 and 4A1/2/3 were preserved at half of the original levels; CYP2C6 and 2C11/2B1/2 were reduced. Enzyme inductions were effective throughout the whole culture period: EROD activity increased fivefold after exposure to phenobarbital (PB) and up to 20-fold after 3-methylcholanthrene (3-MC) exposure; GST activity was stimulated approximately twofold by both inducers. Compound-specific inductions were found for aldrin epoxidase (by PB only), ethoxycoumarin O-deethylase (ECOD) and UDP-glucuronyltransferase (by 3-MC only). Experiments with hepatocyte aggregates showed that the NPC in heterotypic aggregates preserve liver-specific functions more efficiently in long-term experiments. Accordingly, these aggregate cultures from adult rat liver cells could serve as a suitable in vitro model for long-term studies on xenobiotic metabolism or on the interaction of hepatotoxic chemicals with the cross-talk between hepatocytes and NPC.
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PMID:Preservation and inducibility of xenobiotic metabolism in long-term cultures of adult rat liver cell aggregates. 2065 95

Epithelial cells from urinary bladders of pigs were isolated and cultured under serum-free conditions. For these cells it was previously shown that they developed morphologic polarity resembling the epithelium in vivo. Lactate dehydrogenase release was low, chromosome set and activities of marker enzymes (alkaline phosphatase, acid phosphatase, g-glutamyltranspeptidase) were stable over a period of 4 wk. In this study, metabolic competence was evaluated by measuring activities of phase I and phase II enzymes. Activity of prostaglandin H-synthase was expressed in freshly isolated cells as well as in cultured cells, as were activities of the conjugating enzymes glutathione transferase, UDP-glucuronyltransferase and N-acetyltransferase. Cytochrome P4501A1 activity in freshly isolated cells amounted to 10-15% of the respective activity in the porcine liver, this activity was not detectable in cultured cells. No activity was seen in cultured cells after induction with methylcholanthrene and benz[a]anthracene. This cell culture system was used to detect genotoxic effects of substances suspected to induce bladder cancer by measuring the induction of sister chromatid exchanges (SCE). The aromatic amines 4-aminobiphenyl and 2-aminofluorene induced a concentration dependent increase of SCEs at non-cytotoxic concentrations. These results imply that urinary bladder epithelial cells are capable to perform metabolic activation which is required to generate genotoxic effects of aromatic amines. Therefore, this new cell culture system, representing the urinary bladder epithelium, is an effective tool in in vitro toxicology to investigate adverse effects of compounds, regarded or suspected to induce toxic effects in the bladder.
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PMID:An in vitro model of the urinary bladder: cultured porcine urinary bladder epithelial cells. 2065 31

Approximately 7% of all bladder cancer cases in males are associated with occupation. The question arises whether the use of genome-wide association studies was able to identify bladder cancer risk factors that may modulate occupational bladder cancer risk and prognosis. One hundred and forty-three bladder cancer cases with suspected occupational bladder cancer and 337 controls were genotyped for the following polymorphisms: N-acetyltransferase 2 (NAT2), glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), UDP-glucuronyltransferase 1A rs11892031 (UGT1A), rs9642880 (close to c-MYC), and rs710521 (close to TP63). The most relevant polymorphisms for occupational bladder cancer risk were GSTM1 and UGT1A, especially when co-occurring (GSTM1 negative and rs11892031[A/A]: 48% cases vs. 38% controls, OR 1.47, 95% CI 0.99-2.20). The effect was more pronounced in smokers. GSTM1 negative genotype occurred more frequently in cancer cases exposed to aromatic amines, carbolineum, and in painters and varnishers. UGT1A (rs11892031[A/A]) was found frequently in cases exposed to carbolineum, crack test spray, PAH, and in painters and varnishers. All investigated polymorphisms except rs710521 (TP63) seemed to exert an impact on recurrence risk. Relapse-free times were shorter for NAT2 slow and ultra-slow, GSTT1 positive and GSTM1 negative cases. Occupational bladder cancer cases with a number of risk variants displayed significantly shorter relapse-free times compared to cases with few, less relevant risk alleles as evidenced by median difference 8 months. In conclusion, in the present, suspected occupational bladder cancer cases phase II polymorphisms involved in bladder carcinogen metabolism modulate bladder cancer recurrence. Most relevant for bladder cancer risk were GSTM1 and UGT1A but not NAT2.
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PMID:Occupational bladder cancer: Polymorphisms of xenobiotic metabolizing enzymes, exposures, and prognosis. 2869 39


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