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Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report
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Zeitschriftentitel: | Toxicologic Pathology |
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Personen und Körperschaften: | , , , , , , , , , , , , |
In: | Toxicologic Pathology, 31, 2003, 1, S. 60-79 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
SAGE Publications
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Schlagwörter: |
author_facet |
Ittrich, Carina Deml, Erhard Oesterle, Doris Küttler, Karin Mellert, Werner Brendler-Schwaab, Susanne Enzmann, Harald Schladt, Ludwig Bannasch, Peter Haertel, Thomas Mönnikes, Oliver Schwarz, Michael Kopp-Schneider, Annette Ittrich, Carina Deml, Erhard Oesterle, Doris Küttler, Karin Mellert, Werner Brendler-Schwaab, Susanne Enzmann, Harald Schladt, Ludwig Bannasch, Peter Haertel, Thomas Mönnikes, Oliver Schwarz, Michael Kopp-Schneider, Annette |
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author |
Ittrich, Carina Deml, Erhard Oesterle, Doris Küttler, Karin Mellert, Werner Brendler-Schwaab, Susanne Enzmann, Harald Schladt, Ludwig Bannasch, Peter Haertel, Thomas Mönnikes, Oliver Schwarz, Michael Kopp-Schneider, Annette |
spellingShingle |
Ittrich, Carina Deml, Erhard Oesterle, Doris Küttler, Karin Mellert, Werner Brendler-Schwaab, Susanne Enzmann, Harald Schladt, Ludwig Bannasch, Peter Haertel, Thomas Mönnikes, Oliver Schwarz, Michael Kopp-Schneider, Annette Toxicologic Pathology Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report Cell Biology Toxicology Molecular Biology Pathology and Forensic Medicine |
author_sort |
ittrich, carina |
spelling |
Ittrich, Carina Deml, Erhard Oesterle, Doris Küttler, Karin Mellert, Werner Brendler-Schwaab, Susanne Enzmann, Harald Schladt, Ludwig Bannasch, Peter Haertel, Thomas Mönnikes, Oliver Schwarz, Michael Kopp-Schneider, Annette 0192-6233 1533-1601 SAGE Publications Cell Biology Toxicology Molecular Biology Pathology and Forensic Medicine http://dx.doi.org/10.1080/01926230390173888 <jats:p> A rat liver foci bioassay (RLFB) based on an initiation-promotion protocol employing preneoplastic foci of altered hepatocytes (FAH) as an endpoint, was prevalidated in 5 different laboratories. FAH were identified by immunohistochemical demonstration of glutathione- S-transferase (placental form, GSTP) and by staining with hematoxilin/eosin (H&E), and their area fraction was quantified morphometrically. The four model hepatocarcinogens N-nitrosomorpholine, 2-acetylaminofluoren, phenobarbital, and clofibrate were selected according to characteristic differences in their presumed mode of action, and tested in a total of 1,600 male and female rats at 2 different dose levels. The chemicals were found to differ characteristically in their potency and dose-response relationship to induce FAH when given alone or when administered following initiation with diethylnitrosamine. The interlaboratory variation was small for results obtained with the GSTP-stain and somewhat larger with respect to H&E. The assessment of the carcinogenic potential of the four chemicals by the different laboratories was in the same range and the nature of their dose-response relationships did not differ essentially between laboratories. Our results suggest that this RLFB is a sensitive bioassay, providing potentially valuable information for risk assessment including the classification of carcinogenic chemicals according to their mode of action. </jats:p> Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report Toxicologic Pathology |
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10.1080/01926230390173888 |
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Toxicologic Pathology |
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title |
Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_unstemmed |
Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_full |
Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_fullStr |
Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_full_unstemmed |
Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_short |
Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_sort |
prevalidation of a rat liver foci bioassay (rlfb) based on results from 1600 rats: a study report |
topic |
Cell Biology Toxicology Molecular Biology Pathology and Forensic Medicine |
url |
http://dx.doi.org/10.1080/01926230390173888 |
publishDate |
2003 |
physical |
60-79 |
description |
<jats:p> A rat liver foci bioassay (RLFB) based on an initiation-promotion protocol employing preneoplastic foci of altered hepatocytes (FAH) as an endpoint, was prevalidated in 5 different laboratories. FAH were identified by immunohistochemical demonstration of glutathione- S-transferase (placental form, GSTP) and by staining with hematoxilin/eosin (H&E), and their area fraction was quantified morphometrically. The four model hepatocarcinogens N-nitrosomorpholine, 2-acetylaminofluoren, phenobarbital, and clofibrate were selected according to characteristic differences in their presumed mode of action, and tested in a total of 1,600 male and female rats at 2 different dose levels. The chemicals were found to differ characteristically in their potency and dose-response relationship to induce FAH when given alone or when administered following initiation with diethylnitrosamine. The interlaboratory variation was small for results obtained with the GSTP-stain and somewhat larger with respect to H&E. The assessment of the carcinogenic potential of the four chemicals by the different laboratories was in the same range and the nature of their dose-response relationships did not differ essentially between laboratories. Our results suggest that this RLFB is a sensitive bioassay, providing potentially valuable information for risk assessment including the classification of carcinogenic chemicals according to their mode of action. </jats:p> |
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author | Ittrich, Carina, Deml, Erhard, Oesterle, Doris, Küttler, Karin, Mellert, Werner, Brendler-Schwaab, Susanne, Enzmann, Harald, Schladt, Ludwig, Bannasch, Peter, Haertel, Thomas, Mönnikes, Oliver, Schwarz, Michael, Kopp-Schneider, Annette |
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description | <jats:p> A rat liver foci bioassay (RLFB) based on an initiation-promotion protocol employing preneoplastic foci of altered hepatocytes (FAH) as an endpoint, was prevalidated in 5 different laboratories. FAH were identified by immunohistochemical demonstration of glutathione- S-transferase (placental form, GSTP) and by staining with hematoxilin/eosin (H&E), and their area fraction was quantified morphometrically. The four model hepatocarcinogens N-nitrosomorpholine, 2-acetylaminofluoren, phenobarbital, and clofibrate were selected according to characteristic differences in their presumed mode of action, and tested in a total of 1,600 male and female rats at 2 different dose levels. The chemicals were found to differ characteristically in their potency and dose-response relationship to induce FAH when given alone or when administered following initiation with diethylnitrosamine. The interlaboratory variation was small for results obtained with the GSTP-stain and somewhat larger with respect to H&E. The assessment of the carcinogenic potential of the four chemicals by the different laboratories was in the same range and the nature of their dose-response relationships did not differ essentially between laboratories. Our results suggest that this RLFB is a sensitive bioassay, providing potentially valuable information for risk assessment including the classification of carcinogenic chemicals according to their mode of action. </jats:p> |
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spelling | Ittrich, Carina Deml, Erhard Oesterle, Doris Küttler, Karin Mellert, Werner Brendler-Schwaab, Susanne Enzmann, Harald Schladt, Ludwig Bannasch, Peter Haertel, Thomas Mönnikes, Oliver Schwarz, Michael Kopp-Schneider, Annette 0192-6233 1533-1601 SAGE Publications Cell Biology Toxicology Molecular Biology Pathology and Forensic Medicine http://dx.doi.org/10.1080/01926230390173888 <jats:p> A rat liver foci bioassay (RLFB) based on an initiation-promotion protocol employing preneoplastic foci of altered hepatocytes (FAH) as an endpoint, was prevalidated in 5 different laboratories. FAH were identified by immunohistochemical demonstration of glutathione- S-transferase (placental form, GSTP) and by staining with hematoxilin/eosin (H&E), and their area fraction was quantified morphometrically. The four model hepatocarcinogens N-nitrosomorpholine, 2-acetylaminofluoren, phenobarbital, and clofibrate were selected according to characteristic differences in their presumed mode of action, and tested in a total of 1,600 male and female rats at 2 different dose levels. The chemicals were found to differ characteristically in their potency and dose-response relationship to induce FAH when given alone or when administered following initiation with diethylnitrosamine. The interlaboratory variation was small for results obtained with the GSTP-stain and somewhat larger with respect to H&E. The assessment of the carcinogenic potential of the four chemicals by the different laboratories was in the same range and the nature of their dose-response relationships did not differ essentially between laboratories. Our results suggest that this RLFB is a sensitive bioassay, providing potentially valuable information for risk assessment including the classification of carcinogenic chemicals according to their mode of action. </jats:p> Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report Toxicologic Pathology |
spellingShingle | Ittrich, Carina, Deml, Erhard, Oesterle, Doris, Küttler, Karin, Mellert, Werner, Brendler-Schwaab, Susanne, Enzmann, Harald, Schladt, Ludwig, Bannasch, Peter, Haertel, Thomas, Mönnikes, Oliver, Schwarz, Michael, Kopp-Schneider, Annette, Toxicologic Pathology, Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report, Cell Biology, Toxicology, Molecular Biology, Pathology and Forensic Medicine |
title | Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_full | Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_fullStr | Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_full_unstemmed | Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_short | Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
title_sort | prevalidation of a rat liver foci bioassay (rlfb) based on results from 1600 rats: a study report |
title_unstemmed | Prevalidation of a Rat Liver Foci Bioassay (RLFB) Based on Results from 1600 Rats: A Study Report |
topic | Cell Biology, Toxicology, Molecular Biology, Pathology and Forensic Medicine |
url | http://dx.doi.org/10.1080/01926230390173888 |