NASA Human Research Program Investigators' Workshop (2012)
4180.pdf
EFFECTS OF DOSE AND QUALITY OF SPACE-LIKE IONIZING RADIATION ON
CARCINOGENIC TRANSFORMATION IN HUMAN PROSTATE CELLS
B. Dziegielewska1, N. C. K. Valerie1, S. J. Parsons2, J. M. Larner1 and J. Dziegielewski1
1
Department of Radiation Oncology, PO Box 800383 and 2Department of Microbiology, PO Box 800734,
University of Virginia, Charlottesville, VA 22908
The biological mechanism(s) responsible for prostate cancer development and progression
following exposure to radiation is not yet fully known. It is hypothesized that exposure to space ionizing
radiation could increase the risk of tumor development or progression in astronauts. In this work we
established the relationship between the dose and quality (i.e. LET) of space-like radiation and induction
of carcinogenic transformation or progression in prostate cells. Apparently normal human prostate
epithelial cells (RWPE-1) and early stage prostate cancer cells (LNCaP), were exposed to oxygen ions
(200 MeV/n, LET~29 keV/µm), titanium ions (1 GeV/n, LET~125 keV/µM) and protons (1 GeV/n,
LET~0.25 keV/µm) at NASA Space Radiation Laboratory (BNL, Upton, NY), or to X-ray radiation
(LET~2 keV/µm). Surviving cells were tested for increases in tumorigenicity using an anchorageindependent colony formation assay, and the changes in genes and proteins expression evaluated by RTPCR and Western blotting, respectively. We observed a significant and LET- and dose-dependent increase
in the tumorigenicity of irradiated cells. We also observed parallel increases in neurotensin receptor 1
(NTR1) expression in irradiated cells, suggesting that radiation-induced cancer transformation could be
accompanied by NTR1 activation and signal transduction downstream of neurotensin receptor. In
addition, we noted an increase in the expression of ETS family genes and proteins. It is recognized that
changes in ETS gene expression and its fusions could be driving mutations in approximately half of all
prostate cancers. The possible molecular mechanism(s) of carcinogenic transformation in irradiated
prostate cells are discussed. The results obtained during this study will improve our understanding of
biological mechanism(s) of prostate carcinogenesis, and could facilitate the development of novel
countermeasures to protect astronauts health. (This work is supported by NASA grant NNX10AC13G)