Genotoxic risk of ethyl-paraben could be related to telomere shortening

被引：24

作者：

Finot, F. ^{[1
]}

Kaddour, A. ^{[2
]}

Morat, L. ^{[3
]}

Mouche, I. ^{[1
]}

Zaguia, N. ^{[3
]}

Cuceu, C. ^{[3
]}

Souverville, D. ^{[1
]}

Negrault, S. ^{[1
]}

Cariou, O. ^{[1
]}

Essahli, A. ^{[1
]}

Prigent, N. ^{[1
]}

Saul, J. ^{[4
]}

Paillard, F. ^{[1
]}

Heidingsfelder, L. ^{[5
]}

Lafouge, P. ^{[1
]}

Al Jawhari, M.

Hempel, W. M. ^{[3
]}

El May, M. ^{[2
]}

Colicchio, B. ^{[6
]}

Dieterlen, A. ^{[6
]}

Jeandidier, E. ^{[7
]}

Sabatier, L. ^{[3
,8
]}

Clements, J. ^{[4
]}

M'Kacher, R. ^{[3
]}

机构：

[1] Covance Lab, F-78440 Porcheville, France

[2] Tunis El Manar Univ, Sch Med, Tunis, Tunisia

[3] CEA, IRCM, DSV, Radiol & Oncol Lab, Fontenay Aux Roses, France

[4] Covance Labs, Harrogate HG3 1PY, Yorks, England

[5] MetaSystems GmbH, Robert Bosch Str 668804, Altlussheim, Germany

[6] Grp IMTI Univ Haute Alsace, Lab MIPS, F-68093 Mulhouse, France

[7] Serv Genet Grp Hosp Reg Mulhouse & Sud Alsace, F-68070 Mulhouse, France

[8] PROCyTOX Commissariat Energie Atom & Energies Alt, Fontenay Aux Roses, France

来源：

JOURNAL OF APPLIED TOXICOLOGY | 2017年 / 37卷 / 06期

关键词：

ethyl-paraben; metabolic activation; micronucleus; telomere shortening; chromosomal aberrations; HUMAN BREAST-CANCER; PERIPHERAL-BLOOD LYMPHOCYTES; MOUSE LYMPHOMA-CELLS; ENVIRONMENTAL ESTROGENS; CHROMOSOMAL INSTABILITY; GENOME INSTABILITY; MICRONUCLEUS ASSAY; MUTATION ASSAY; HISTONE H2AX; HUMAN HEALTH;

D O I：

10.1002/jat.3425

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

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 (3h) in the presence of S9 and a long exposure (26h) 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 (c) 2016 John Wiley & Sons, Ltd.

引用

页码：758 / 771

页数：14

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