Cell Type-dependent Gene Transcription Profile in Three Dimensional Human Skin Tissue Model Exposed to Low Doses of Ionizing Radiation: Implications for Medical Exposures
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.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 1039108
- Report Number(s):
- PNNL-SA-79289; EMMUEG; 400409900; TRN: US201209%%171
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 53, Issue 4; ISSN 0893-6692
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
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