Sex and tissue-specific differences in low-dose radiation-induced oncogenic signaling.
OBJECTIVE
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.


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.
Besplug
Jill
J
Department of Biological Sciences, University of Lethbridge, Alberta, Canada.
Burke
Paula
P
Ponton
André
A
Filkowski
Jody
J
Titov
Viktor
V
Kovalchuk
Igor
I
Kovalchuk
Olga
O
D000222:Adaptation, Physiological / Q000528:radiation effects; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D008099:Liver / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism* / Q000528:radiation effects; D009363:Neoplasm Proteins / Q000378:metabolism*; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism*; D009928:Organ Specificity / Q000528:radiation effects; D011829:Radiation Dosage; D015398:Signal Transduction / Q000528:radiation effects*; D013154:Spleen / Q000378:metabolism* / Q000528:radiation effects; D014018:Tissue Distribution
D009363:Neoplasm Proteins