Species- and sex-specific renal cytotoxicity of Ochratoxin A and B in vitro

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2001
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O'Brien, Evelyn
Stack, Michael E.
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Experimental and Toxicologic Pathology. 2001, 53(2-3), pp. 215-225. ISSN 0940-2993. Available under: doi: 10.1078/0940-2993-00184
Zusammenfassung

Four different cell models were chosen for comparison of OTA and OTB toxicity: primary porcine (PKC), rat (RPTC) and human renal proximal epithelial cells (HKC) from both sexes and a porcine renal cell line: LLC-PK1. Culture conditions were tested and optimized for each respective cell type (species/sex and origin). All cell types were characterized for epithelial origin and growth patterns and following optimization of dosing strategies and assay procedures, a strict study design was implemented to avoid systemic variations. Due to possible sensitivity differences, three simple endpoints were chosen to provide basic data for interspecies comparison: neutral red uptake, MTT reduction and cell number. Of the endpoints tested neutral red appeared the most sensitive, although all three parameters yielded comparable EC 50's. Sex-differences were observed between male and female HKC cells following 96 h exposure to OTA, with HKC(m) being more sensitive than HKC(f). No sex-difference was observed in PKC cells, however, the PKC were approximately 3 and 10 times more sensitive than HKC(m) and HKC(f), respectively, to OTA and OTB. Interestingly, the CI 95 of the EC 50 values obtained for OTA (15.5 16.5 μM) and OTB (17.0 21.0 μM) were comparable in the PKC cells. In contrast, OTB had lower cytotoxicity than OTA in HKC and LLC-PK1 (approx. 2-fold) and no effects in RPTC. Overall, HKC(m) were nearly as sensitive as PKC towards OTA, followed by RPTC, LLC-PK1 and HKC(f), thus suggesting a sex specific sensitivity in humans towards OTA induced cytotoxicity.

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570 Biowissenschaften, Biologie
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Ochratoxin, cytotoxicity, in vitro
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ISO 690DIETRICH, Daniel R., Evelyn O'BRIEN, Michael E. STACK, Alexandra H. HEUSSNER, 2001. Species- and sex-specific renal cytotoxicity of Ochratoxin A and B in vitro. In: Experimental and Toxicologic Pathology. 2001, 53(2-3), pp. 215-225. ISSN 0940-2993. Available under: doi: 10.1078/0940-2993-00184
BibTex
@article{Dietrich2001Speci-8709,
  year={2001},
  doi={10.1078/0940-2993-00184},
  title={Species- and sex-specific renal cytotoxicity of Ochratoxin A and B in vitro},
  number={2-3},
  volume={53},
  issn={0940-2993},
  journal={Experimental and Toxicologic Pathology},
  pages={215--225},
  author={Dietrich, Daniel R. and O'Brien, Evelyn and Stack, Michael E. and Heussner, Alexandra H.}
}
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    <dcterms:abstract xml:lang="eng">Four different cell models were chosen for comparison of OTA and OTB toxicity: primary porcine (PKC), rat (RPTC) and human renal proximal epithelial cells (HKC) from both sexes and a porcine renal cell line: LLC-PK1. Culture conditions were tested and optimized for each respective cell type (species/sex and origin). All cell types were characterized for epithelial origin and growth patterns and following optimization of dosing strategies and assay procedures, a strict study design was implemented to avoid systemic variations. Due to possible sensitivity differences, three simple endpoints were chosen to provide basic data for interspecies comparison: neutral red uptake, MTT reduction and cell number. Of the endpoints tested neutral red appeared the most sensitive, although all three parameters yielded comparable EC 50's. Sex-differences were observed between male and female HKC cells following 96 h exposure to OTA, with HKC(m) being more sensitive than HKC(f). No sex-difference was observed in PKC cells, however, the PKC were approximately 3 and 10 times more sensitive than HKC(m) and HKC(f), respectively, to OTA and OTB. Interestingly, the CI 95 of the EC 50 values obtained for OTA (15.5 16.5 μM) and OTB (17.0 21.0 μM) were comparable in the PKC cells. In contrast, OTB had lower cytotoxicity than OTA in HKC and LLC-PK1 (approx. 2-fold) and no effects in RPTC. Overall, HKC(m) were nearly as sensitive as PKC towards OTA, followed by RPTC, LLC-PK1 and HKC(f), thus suggesting a sex specific sensitivity in humans towards OTA induced cytotoxicity.</dcterms:abstract>
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