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p53 induction as a genotoxic test for twenty-five chemicals undergoing in vivo carcinogenicity testing.

In vivo carcinogenicity testing is an expensive and time-consuming process, and as a result, only a relatively small fraction of new and existing chemicals has been tested in this manner. Therefore, the development and validation of alternative approaches is desirable. We previously developed a mamm...

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Autores principales: Duerksen-Hughes, P J, Yang, J, Ozcan, O
Formato: Texto
Lenguaje:English
Publicado: 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566603/
https://www.ncbi.nlm.nih.gov/pubmed/10504146
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author Duerksen-Hughes, P J
Yang, J
Ozcan, O
author_facet Duerksen-Hughes, P J
Yang, J
Ozcan, O
author_sort Duerksen-Hughes, P J
collection PubMed
description In vivo carcinogenicity testing is an expensive and time-consuming process, and as a result, only a relatively small fraction of new and existing chemicals has been tested in this manner. Therefore, the development and validation of alternative approaches is desirable. We previously developed a mammalian in vitro assay for genotoxicity based on the ability of cells to increase their level of the tumor-suppressor protein p53 in response to DNA damage. Cultured cells are treated with various amounts of the test substances, and at defined times following treatment, they are harvested and lysed. The lysates are analyzed for p53 by Western blot and/or enzyme-linked immunosorbent assay analysis. An increase in cellular p53 following treatment is interpreted as evidence for DNA damage. To determine the ability of this p53-induction assay to predict carcinogenicity in rodents and to compare such results with those obtained using alternate approaches, we subjected 25 chemicals from the predictive toxicology evaluation 2 list to analysis with this method. Five substances (citral, cobalt sulfate heptahydrate, D&C Yellow No. 11, oxymetholone, and t-butylhydroquinone) tested positive in this assay, and three substances (emodin, phenolphthalein, and sodium xylenesulfonate) tested as possibly positive. Comparisons between the results obtained with this assay and those obtained with the in vivo protocol, the Salmonella assay, and the Syrian hamster embryo (SHE) cell assay indicate that the p53-induction assay is an excellent predictor of the limited number of genotoxic carcinogens in this set, and that its accuracy is roughly equivalent to or better than the Salmonella and SHE assays for the complete set of chemicals.
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spelling pubmed-15666032006-09-19 p53 induction as a genotoxic test for twenty-five chemicals undergoing in vivo carcinogenicity testing. Duerksen-Hughes, P J Yang, J Ozcan, O Environ Health Perspect Research Article In vivo carcinogenicity testing is an expensive and time-consuming process, and as a result, only a relatively small fraction of new and existing chemicals has been tested in this manner. Therefore, the development and validation of alternative approaches is desirable. We previously developed a mammalian in vitro assay for genotoxicity based on the ability of cells to increase their level of the tumor-suppressor protein p53 in response to DNA damage. Cultured cells are treated with various amounts of the test substances, and at defined times following treatment, they are harvested and lysed. The lysates are analyzed for p53 by Western blot and/or enzyme-linked immunosorbent assay analysis. An increase in cellular p53 following treatment is interpreted as evidence for DNA damage. To determine the ability of this p53-induction assay to predict carcinogenicity in rodents and to compare such results with those obtained using alternate approaches, we subjected 25 chemicals from the predictive toxicology evaluation 2 list to analysis with this method. Five substances (citral, cobalt sulfate heptahydrate, D&C Yellow No. 11, oxymetholone, and t-butylhydroquinone) tested positive in this assay, and three substances (emodin, phenolphthalein, and sodium xylenesulfonate) tested as possibly positive. Comparisons between the results obtained with this assay and those obtained with the in vivo protocol, the Salmonella assay, and the Syrian hamster embryo (SHE) cell assay indicate that the p53-induction assay is an excellent predictor of the limited number of genotoxic carcinogens in this set, and that its accuracy is roughly equivalent to or better than the Salmonella and SHE assays for the complete set of chemicals. 1999-10 /pmc/articles/PMC1566603/ /pubmed/10504146 Text en
spellingShingle Research Article
Duerksen-Hughes, P J
Yang, J
Ozcan, O
p53 induction as a genotoxic test for twenty-five chemicals undergoing in vivo carcinogenicity testing.
title p53 induction as a genotoxic test for twenty-five chemicals undergoing in vivo carcinogenicity testing.
title_full p53 induction as a genotoxic test for twenty-five chemicals undergoing in vivo carcinogenicity testing.
title_fullStr p53 induction as a genotoxic test for twenty-five chemicals undergoing in vivo carcinogenicity testing.
title_full_unstemmed p53 induction as a genotoxic test for twenty-five chemicals undergoing in vivo carcinogenicity testing.
title_short p53 induction as a genotoxic test for twenty-five chemicals undergoing in vivo carcinogenicity testing.
title_sort p53 induction as a genotoxic test for twenty-five chemicals undergoing in vivo carcinogenicity testing.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566603/
https://www.ncbi.nlm.nih.gov/pubmed/10504146
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