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Patterns of gene expressions induced by arsenic trioxide in cultured human fibroblasts
Vanina Burnichon1, Séverine Jean, Laurence Bellon
1Laboratoire de Biogénotoxicologie et Mutagenèse Environnementale (EA 1784-IFR PMSE 112), Faculté de Médecine, Université de la Méditerranée, 27 boulevard Jean Moulin, 13385 cedex 05, Marseille, France.
Abstract:
Arsenic exposure is associated with several human diseases and particularly, with neoplasia. Although the mechanism of arsenic toxicity is not fully understood, several recent works pointed out the involvement of oxidative stress in arsenic-induced DNA damage that, in living cells, correlates with changes in gene expressions. In cultured human fibroblasts exposed for 24 h to micromolar arsenic concentrations, we studied, using real-time RT-PCR, the expression profile of a limited number of genes: genes coding for a stress protein (HSP70), transcription factors (cJUN, cFOS, ETR103, ETR101 and TTP) and cell cycle or DNA repair proteins (P21, GADD153). We observed that the expression profile of genes followed individual different patterns that can be summed up in early-transient gene expression by contrast to delayed gene expression.
Insights
Arsenic exposure can alter gene expression in human cells, potentially leading to disease. This study observed distinct early-transient and delayed gene expression patterns in fibroblasts after arsenic exposure.
Area of Science:
- Toxicology
- Molecular Biology
- Genetics
Background:
- Arsenic exposure is linked to human diseases, including cancer.
- Oxidative stress and DNA damage are implicated in arsenic toxicity.
- Arsenic exposure affects gene expression in living cells.
Purpose of the Study:
- To investigate the gene expression profile in human fibroblasts exposed to arsenic.
- To understand the temporal patterns of gene expression changes following arsenic exposure.
Main Methods:
- Cultured human fibroblasts were exposed to micromolar arsenic concentrations for 24 hours.
- Real-time RT-PCR was used to analyze the expression of specific genes.
- Genes studied included those for stress proteins (HSP70), transcription factors (cJUN, cFOS, ETR103, ETR101, TTP), and cell cycle/DNA repair proteins (P21, GADD153).
Main Results:
- Arsenic exposure induced varied gene expression patterns in individual cells.
- Observed patterns included early-transient gene expression.
- Delayed gene expression patterns were also identified.
Conclusions:
- Arsenic exposure significantly impacts gene expression in human fibroblasts.
- Distinct temporal profiles of gene expression (early-transient vs. delayed) occur in response to arsenic.
- These findings contribute to understanding arsenic toxicity mechanisms and its link to neoplasia.
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