Proteomic analysis of low dose arsenic and ionizing radiation exposure on keratinocytes

Berglund, Susanne R.; Santana, Alison; Li, Dan; Rice, Robert H.; Rocke, David M.; Goldberg, Zelanna

doi:10.1002/pmic.200800118

Cited by 18 publications

(13 citation statements)

References 42 publications

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“…Interestingly, some proteins were shown to be modulated by doses as low as 1 cGy and 0.1 Gy of LDIR exposures in human keratinocytes [ 34 ]. Among these protein changes the authors observed the induction of HINT1 and the repression of HSP27 [ 34 ]. In future studies it would be interesting to determine if these protein changes were accompanied by mRNA expression alterations.…”

Section: Gene Expression Changes In Human Cells Following Low Dosementioning

confidence: 99%

Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

Sokolov

Neumann

2015

IJMS

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Exposure to ionizing radiation (IR) is inevitable to humans in real-life scenarios; the hazards of IR primarily stem from its mutagenic, carcinogenic, and cell killing ability. For many decades, extensive research has been conducted on the human cell responses to IR delivered at a low dose/low dose (LD) rate. These studies have shown that the molecular-, cellular-, and tissue-level responses are different after low doses of IR (LDIR) compared to those observed after a short-term high-dose IR exposure (HDIR). With the advent of high-throughput technologies in the late 1990s, such as DNA microarrays, changes in gene expression have also been found to be ubiquitous after LDIR. Very limited subset of genes has been shown to be consistently up-regulated by LDIR, including CDKN1A. Further research on the biological effects and mechanisms induced by IR in human cells demonstrated that the molecular and cellular processes, including transcriptional alterations, activated by LDIR are often related to protective responses and, sometimes, hormesis. Following LDIR, some distinct responses were observed, these included bystander effects, and adaptive responses. Changes in gene expression, not only at the level of mRNA, but also miRNA, have been found to crucially underlie these effects having implications for radiation protection purposes.

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Section: Gene Expression Changes In Human Cells Following Low Dosementioning

confidence: 99%

Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

Sokolov

Neumann

2015

IJMS

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“…The proteomic responses observed with metals, metalloids, and their organic derivatives are similar to the ones observed with small organic molecules (Table ). HSPs are found modulated in more than half of the papers . Enolase is also found modulated frequently , as well as ER stress , proteasome , or peroxiredoxins .…”

Section: Proteomics For Studying Biological Responses To Toxicantsmentioning

confidence: 99%

Proteomics in mechanistic toxicology: History, concepts, achievements, caveats, and potential

Rabilloud

Lescuyer

2014

Proteomics

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Toxicoproteomics can be defined as the application of proteomic approaches to the understanding of toxicology problems, and this review deals with the various types of applications that have been described in the literature. Toxicoproteomics has been applied to very different classes of toxicants, from drugs and natural products to metals, or from industrial chemicals to nanoparticles and nanofibers. It has also been applied to address questions at different levels, from the search of the primary molecular targets of toxicants to the deciphering of the molecular responses of cells and tissues to toxicants. Although restricted to mammalian cells and tissues, this paper reviews these two levels of investigation and the different application areas of toxicoproteomics, leading to the discussion of the advantages and drawbacks of the most popular proteomic platforms. Some of the pending questions in toxicoproteomics are also critically addressed, such as the specificity, validation, and result hierarchization issues. The question of shared mechanisms, which are encountered in many toxicoproteomic papers dealing with different toxicants, is also discussed. Finally, the future of toxicoproteomics is briefly outlined.

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“…In connection with additional funding, we studied the proteomic interaction between oxidative damage from low dose radiation and from arsenic exposure (Berglund et al 2009). We identified proteins that were differentially responsive to LDIR and arsenic, which helps elucidate the different responses to stimuli which share many common features.…”

Section: Other Areasmentioning

confidence: 99%

Genome Wide Evaluation of Normal Human Tissue in Response to Controlled, In vivo Low-Dose Low LET Ionizing Radiation Exposure: Pathways and Mechanisms Final Report, September 2013

Rocke¹

2013

Self Cite

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During course of this project, we have worked in several areas relevant to low-dose ionizing radiation. In-Vivo Human Time Course DataWe have three papers from data derived from the human in-vivo low-dose studies, two published and one still under review. The first (Goldberg et al. 2005) evaluated differences in gene expression due to dose. Human skin samples from men exposed to 0, 1, 10, and 100 cGy during the initial radiotherapy treatment for prostate cancer were analyzed for gene expression using the Affymetrix HGU133 Plus 2.0 platform. This study was funded under the predecessor grant to this one (DOE DE-FG03-01ER63237), as were several important methods papers that were used in the subsequent projects from the present grant. These included Berglund et al. (2007) The second (Berglund et al. 2008) examined transient changes in expression over time from a low dose. Using the same protocol and analysis methods, we analyzed nineteen gene groups and seven pathways for transient response, defined here as a transcriptional response that is elevated or depressed at 3 and 8 hours compared to the baseline at 0, and at 24 hours. We found nine gene groups that showed such transient differential expression.The third (Kalanetra et al. 2013) is a more detailed examination of time-course behavior of gene expression from in-vivo exposed skin. In this new data set, we have split observations at 0, 3, 8, and 24 hours post irradiation by 10cGy (eight samples per subject) and eight patients with usable samples. We obtained comprehensive gene expression data using the Illumina platform and utilizing a complex data analysis strategy we obtained 1766 differentially expressed genes. We found that pathways associated with apoptosis and survival, development, cell adhesion, DNA damage, immune response, signal transduction, cytoskeleton remodeling, G-protein signaling, cCTP/CTP and cUTP/UTP metabolism, cell cycle, ATP and ITP metabolism, GTP and XTP metabolism, and CFTR folding and maturation were all significantly affected. This is in review. MatTek EpiDermFT Skin PlugsDespite being widely investigated, cell lines grown as monolayers provide a limited insight on the biological processes occurring under a given condition. EpiDermFT is a three-dimensional skin model which is composed of normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF). This skin model is mainly utilized for studying human skin responses to cosmetics and topical agents. We

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Proteomic analysis of low dose arsenic and ionizing radiation exposure on keratinocytes

Cited by 18 publications

References 42 publications

Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

Proteomics in mechanistic toxicology: History, concepts, achievements, caveats, and potential

Genome Wide Evaluation of Normal Human Tissue in Response to Controlled, In vivo Low-Dose Low LET Ionizing Radiation Exposure: Pathways and Mechanisms Final Report, September 2013

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