Document Detail

Sex and tissue-specific differences in low-dose radiation-induced oncogenic signaling.
MedLine Citation:
PMID:  16019925     Owner:  NLM     Status:  MEDLINE    
PURPOSE: The possible adverse health effects of low-dose radiation (LDR) exposure constitute a growing concern. Clinically and environmentally relevant exposures occur predominantly under chronic conditions, notwithstanding that most studies of LDR effects have been performed using a single acute exposure. Sex- and tissue-specificity of the LDR-induced changes have not been considered before. We investigated LDR-related expression patterns in muscle, liver and spleen of male and female mice subjected to acute and chronic LDR exposure. Genes involved in oncogenic signaling were of specific interest, as radiation is a well-known carcinogen. MATERIALS AND METHODS: We analyzed the expression pattern of genes coding for growth factors and growth-factor receptors, cytoplasmic serine/threonine protein kinases, G-proteins and nuclear DNA-binding proteins, and other important components of oncogenic signaling. RESULTS: We found sex- and tissue-specific changes in the expression of Ras superfamily members (Nras, Rab2, Rab34, Vav2), protein kinase C (PKC) isoforms (PKCbeta, PKCmu), AP-1 factor components (Jun, JunB and FosB), Wnt signaling pathway members as well as in a variety of other cellular proto-oncogenes and oncogenes. Importantly, Western blot analysis of JunB, PKCmu and Rab2 proteins supported the transcriptomic data. CONCLUSIONS: Substantially different protein levels were observed in all three tissues (muscle, spleen and liver) of acutely and chronically irradiated female and male animals. Based on the obtained data and available literature, we discuss several possible mechanisms that may contribute to radiation-induced carcinogenesis in various tissues of males and females. From our results we could identify the genes that may serve as sex- and tissue-specific biomarkers of the LDR exposure.
Jill Besplug; Paula Burke; André Ponton; Jody Filkowski; Viktor Titov; Igor Kovalchuk; Olga Kovalchuk
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation biology     Volume:  81     ISSN:  0955-3002     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-07-19     Completed Date:  2005-08-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  157-68     Citation Subset:  IM; S    
Department of Biological Sciences, University of Lethbridge, Alberta, Canada.
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MeSH Terms
Adaptation, Physiological / radiation effects
Dose-Response Relationship, Radiation
Gene Expression Regulation, Neoplastic / radiation effects*
Liver / metabolism*,  radiation effects
Mice, Inbred C57BL
Muscles / metabolism*,  radiation effects
Neoplasm Proteins / metabolism*
Neoplasms, Radiation-Induced / metabolism*
Organ Specificity / radiation effects
Radiation Dosage
Signal Transduction / radiation effects*
Spleen / metabolism*,  radiation effects
Tissue Distribution
Reg. No./Substance:
0/Neoplasm Proteins

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