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Title: Cell Type-dependent Gene Transcription Profile in Three Dimensional Human Skin Tissue Model Exposed to Low Doses of Ionizing Radiation: Implications for Medical Exposures

Abstract

The concern over possible health risks from exposures to low doses of ionizing radiation has been driven largely by the increase in medical exposures, the routine implementation of X-ray backscatter devices for airport security screening, and, most recently, the nuclear incident in Japan. Due to a paucity of direct epidemiological data at very low doses, cancer risk must be estimated from high dose exposure scenarios. However, there is increasing evidence that low and high dose exposures result in different signaling events and may have different mechanisms of cancer induction. We have examined the radiation induced temporal response of an in vitro three dimensional (3D) human skin tissue model using microarray-based transcriptional profiling. Our data shows that exposure to 100 mGy of X-rays is sufficient to affect gene transcription. Cell type specific analysis showed significant changes in gene expression with the levels of > 1400 genes altered in the dermis and > 400 genes regulated in the epidermis. The two cell types rarely exhibited overlapping responses at the mRNA level. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) measurements validated the microarray data in both regulation direction and value. Key pathways identified relate to cell cycle regulation, immune responses, hypoxia, reactive oxygenmore » signaling, and DNA damage repair. We discuss in particular the role of proliferation and emphasizing how the disregulation of cellular signaling in normal tissue may impact progression towards radiation induced secondary diseases.« less

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1039108
Report Number(s):
PNNL-SA-79289
Journal ID: ISSN 0893-6692; EMMUEG; 400409900; TRN: US201209%%171
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Environmental and Molecular Mutagenesis
Additional Journal Information:
Journal Volume: 53; Journal Issue: 4; Journal ID: ISSN 0893-6692
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; ANOXIA; CELL CYCLE; DISEASES; DNA DAMAGES; EPIDERMIS; GENES; IN VITRO; INDUCTION; IONIZING RADIATIONS; LOW DOSE IRRADIATION; NEOPLASMS; OXYGEN; POLYMERASE CHAIN REACTION; RADIATIONS; REPAIR; TRANSCRIPTION; BACKSCATTERING

Citation Formats

Freiin von Neubeck, Claere H, Shankaran, Harish, Karin, Norman J, Kauer, Paula M, Chrisler, William B, Wang, Xihai, Robinson, Robert J, Waters, Katrina M, Tilton, Susan C, and Sowa, Marianne B. Cell Type-dependent Gene Transcription Profile in Three Dimensional Human Skin Tissue Model Exposed to Low Doses of Ionizing Radiation: Implications for Medical Exposures. United States: N. p., 2012. Web. doi:10.1002/em.21682.
Freiin von Neubeck, Claere H, Shankaran, Harish, Karin, Norman J, Kauer, Paula M, Chrisler, William B, Wang, Xihai, Robinson, Robert J, Waters, Katrina M, Tilton, Susan C, & Sowa, Marianne B. Cell Type-dependent Gene Transcription Profile in Three Dimensional Human Skin Tissue Model Exposed to Low Doses of Ionizing Radiation: Implications for Medical Exposures. United States. https://doi.org/10.1002/em.21682
Freiin von Neubeck, Claere H, Shankaran, Harish, Karin, Norman J, Kauer, Paula M, Chrisler, William B, Wang, Xihai, Robinson, Robert J, Waters, Katrina M, Tilton, Susan C, and Sowa, Marianne B. 2012. "Cell Type-dependent Gene Transcription Profile in Three Dimensional Human Skin Tissue Model Exposed to Low Doses of Ionizing Radiation: Implications for Medical Exposures". United States. https://doi.org/10.1002/em.21682.
@article{osti_1039108,
title = {Cell Type-dependent Gene Transcription Profile in Three Dimensional Human Skin Tissue Model Exposed to Low Doses of Ionizing Radiation: Implications for Medical Exposures},
author = {Freiin von Neubeck, Claere H and Shankaran, Harish and Karin, Norman J and Kauer, Paula M and Chrisler, William B and Wang, Xihai and Robinson, Robert J and Waters, Katrina M and Tilton, Susan C and Sowa, Marianne B},
abstractNote = {The concern over possible health risks from exposures to low doses of ionizing radiation has been driven largely by the increase in medical exposures, the routine implementation of X-ray backscatter devices for airport security screening, and, most recently, the nuclear incident in Japan. Due to a paucity of direct epidemiological data at very low doses, cancer risk must be estimated from high dose exposure scenarios. However, there is increasing evidence that low and high dose exposures result in different signaling events and may have different mechanisms of cancer induction. We have examined the radiation induced temporal response of an in vitro three dimensional (3D) human skin tissue model using microarray-based transcriptional profiling. Our data shows that exposure to 100 mGy of X-rays is sufficient to affect gene transcription. Cell type specific analysis showed significant changes in gene expression with the levels of > 1400 genes altered in the dermis and > 400 genes regulated in the epidermis. The two cell types rarely exhibited overlapping responses at the mRNA level. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) measurements validated the microarray data in both regulation direction and value. Key pathways identified relate to cell cycle regulation, immune responses, hypoxia, reactive oxygen signaling, and DNA damage repair. We discuss in particular the role of proliferation and emphasizing how the disregulation of cellular signaling in normal tissue may impact progression towards radiation induced secondary diseases.},
doi = {10.1002/em.21682},
url = {https://www.osti.gov/biblio/1039108}, journal = {Environmental and Molecular Mutagenesis},
issn = {0893-6692},
number = 4,
volume = 53,
place = {United States},
year = {Tue Apr 17 00:00:00 EDT 2012},
month = {Tue Apr 17 00:00:00 EDT 2012}
}