Arsenic exposure causes epigenetic dysregulation of IL-8 expression leading to proneoplastic changes in kidney cells.
Toxicol Lett
; 237(1): 1-10, 2015 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-26008221
ABSTRACT
Prolonged arsenic exposure has been shown to cause several detrimental effects in adults. However its effects following prenatal exposure are not well defined at the epigenetic level, particularly in terms of changes which may predispose an individual to adult malignancies. In this work, we have studied the effect of arsenic exposure on renal system using human embryonic kidney cells and prenatally exposed animals and identified Interleukin-8(IL-8) and its homologue (CINC-1) as mediators of arsenic induced renal toxicity. We further show that embryonic kidney cells are more responsive to arsenic leading to higher induction of IL-8 as compared to adult cells due to DNA methylation and histone acetylation (H3 acetylation) changes in the IL-8 promoter. Through bisulfite analysis of the IL-8 promoter, we have also identified an arsenic modulated CpG site at -168 bases upstream of transcription start site. This CpG is associated with C/EBP and CREB binding sites in the IL-8 promoter and its demethylation by arsenic coupled with increased H3 histone acetylation and CBP/P300 recruitment could lead to induction of IL-8. Our study shows how epigenetic modulation of IL-8 by arsenic could contribute to increased cell migratory and proliferative capabilities, cell cycle dysregulation and renal toxicity.
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Base de dados:
MEDLINE
Assunto principal:
Arsênio
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Interleucina-8
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Epigênese Genética
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Células Epiteliais
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Rim
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article