Glutathione S-transferase polymorphisms and ochratoxin A toxicity in primary human urothelial cells
| Autor: | Klaus Golka, Harald Schulze, Stefan Lebrun, Wolfram Föllmann |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Ochratoxin A Genotype DNA damage Biology Toxicology medicine.disease_cause Nephrectomy chemistry.chemical_compound GSTP1 medicine Humans Ochratoxin Cells Cultured Carcinogen Aged Glutathione Transferase Aged 80 and over Polymorphism Genetic Reverse Transcriptase Polymerase Chain Reaction DNA Middle Aged Ochratoxins Isoenzymes Comet assay Glutathione S-transferase chemistry Biochemistry Carcinogens biology.protein Female Comet Assay Urothelium Genotoxicity DNA Damage |
| Zdroj: | Toxicology. 224:81-90 |
| ISSN: | 0300-483X |
| Popis: | The mycotoxin ochratoxin A (OTA) is a worldwide contaminant of human food. OTA is genotoxic, immunotoxic, teratogenic and carcinogenic in rodents and can cause nephropathy in pigs. High amounts of OTA can cause nephropathy in humans. Moreover, evidence has been accumulated that OTA is a genotoxic carcinogen. Nevertheless, the mechanism that leads to OTA toxicity has not been fully resolved and it is discussed if a bioactivation of OTA is necessary or not. In this study the genotoxicity of OTA was investigated in primary human urothelial cells by means of alkaline single cell gel electrophoresis (Comet assay). Primary cultured human urothelial cells derived from tissue specimens of urological patients were incubated with 100 microM OTA for 3 h. In contrast to recently published results in MDCK cell lines, the cell cultures showed great interindividual differences in the extent of DNA damage. To evaluate these great interindividual differences the influence of the genotype of the isoenzymes of glutathione S-transferase (GST), namely GSTT1, GSTM1 and GSTP1 on the genotoxic potential of OTA was examined. The genotypes of these polymorphic enzymes were determined by polymerase chain reaction (PCR) and the distributions of the genotypes were correlated with the extent of DNA damage. We found associations between the genotypes of the polymorphic GST isoenzymes and the extent of DNA damage between subgroups with and without OTA-related DNA damage. From these results we conclude that genetic predisposition has the potential to influence OTA genotoxicity. |
| Databáze: | OpenAIRE |
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