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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
Genotoxic risk of ethyl-paraben could be related to telomere shortening
Journal of Applied Toxicology, Volume 37, No. 6, Year 2017
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Description
The ability of parabens to promote the appearance of multiple cancer hallmarks in breast epithelium cells provides grounds for regulatory review of the implication of the presence of parabens in human breast tissue. It is well documented that telomere dysfunction plays a significant role in the initiation of genomic instability during carcinogenesis in human breast cancer. In the present study, we evaluated the genotoxic effect of ethyl 4-hydroxybenzoate (ethyl-paraben), with and without metabolic activation (S9), in studies following OECD guidelines. We observed a significant increase in genotoxic damage using the Mouse Lymphoma Assay and in vitro micronucleus (MN) tests in the L5178Y cell line in the presence of S9 only after a short exposure. A high frequency of MN was observed in the TK6 cells after a short exposure (3 h) in the presence of S9 and a long exposure (26 h) without S9. We found significant increases in the MN frequency and induced chromosomal aberrations in the lymphocytes of only one donor after ethyl-paraben exposure in the presence of S9 after a short exposure. Cytogenetic characterization of the paraben-treated cells demonstrated telomere shortening associated with telomere loss and telomere deletions in L5178Y and TK6 cells and lymphocytes of the paraben sensitive-donor. In a control cohort of 68 human lymphocytes, telomere length and telomere aberrations were age-dependent and showed high inter-individual variation. This study is the first to link telomere shortening and the genotoxic effect of ethyl paraben in the presence of S9 and raises the possibility that telomere shortening may be a proxy for underlying inter-individual sensitivity to ethyl-paraben. Copyright © 2016 John Wiley & Sons, Ltd.
Authors & Co-Authors
Finot, Francis
France
Covance Laboratory
France, Paris
Cell Environment
Kaddour, Akram
France, Paris
Cell Environment
Tunisia, Tunis
Université de Tunis el Manar
Morat, Luc
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
Mouche, Isabelle
France
Covance Laboratory
France, Paris
Cell Environment
Zaguia, Narjes
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
Cuceu, Corina
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
Souverville, D.
France
Covance Laboratory
Négrault, S.
France
Covance Laboratory
Cariou, Olivier
France
Covance Laboratory
Essahli, A.
France
Covance Laboratory
Prigent, N.
France
Covance Laboratory
Saul, Jim
United Kingdom, Suffolk
Covance Laboratories Limited
Paillard, Françoise
France
Covance Laboratory
Heidingsfelder, Leonhard
Germany, Altlussheim
Metasystems
Lafouge, P.
France
Covance Laboratory
Al-Jawhari, Mustafa
France, Paris
Cell Environment
Hempel, William M.
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
El-May, Michèle Véronique
Tunisia, Tunis
Université de Tunis el Manar
Colicchio, Bruno
France, Mulhouse
Universite de Haute Alsace
Dieterlen, Alain
France, Mulhouse
Universite de Haute Alsace
Jeandidier, Éric
France, Mulhouse
Groupe Hospitalier de la Région Mulhouse Sud Alsace
Sabatier, Laure
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
France, Gif-sur-yvette
Commissariat a L'energie Atomique et Aux Energies Alternatives
Clements, Julie
United Kingdom, Suffolk
Covance Laboratories Limited
M'Kacher, Radhia
France, Paris
Cell Environment
France, Fontenay-aux-roses
Cea Fontenay Aux Roses
Statistics
Citations: 24
Authors: 24
Affiliations: 9
Identifiers
Doi:
10.1002/jat.3425
ISSN:
0260437X
e-ISSN:
10991263
Research Areas
Cancer
Noncommunicable Diseases
Study Design
Cohort Study