22nd Annual NASA Space Radiation Investigators' Workshop (2011)
7057.pdf
Effects of Heavy Ion Radiation on Carcinogenic Transformation and
Neuroendocrine Differentiation in Human Prostate Cells
Nicholas C. K. Valerie1, James M. Larner1, Sarah J. Parsons2 & Jaroslaw Dziegielewski1*
(1) Department of Radiation Oncology, University of Virginia, Charlottesville, VA
(2) Department of Microbiology, University of Virginia, Charlottesville, VA
Prostate cancer is the most often diagnosed type of cancer in male astronauts, as well
as the most common cancer and leading cause of cancer deaths in men. However, the
biological mechanism(s) responsible for prostate cancer development and progression
following exposure to radiation is not yet known. It is believed that exposure to space
radiation could increase the risk of tumor development or progression. We hypothesize that
space radiation would not only directly induce neoplastic transformation in prostate cells, but
could also stimulate surrounding cells and tissues to provide growth assistance to the tumor.
One of the possible mechanisms of such stimulation is neuroendocrine differentiation: the
converting of normal epithelial cells into neuroendocrine-like cells which, produce hormones
and growth factors. Apparently normal human prostate cells and prostate cancer cells, were
exposed to oxygen ions (220 MeV/n, LET~25 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 a soft agar assay and neuroendocrine differentiation using the
expression of specific markers. We observed a significant and dose-dependent increase in the
tumorigenicity of cells irradiated with a single dose of heavy ions but not neuroendocrine
differentiation. However, neuroendocrine differentiation occurred following fractionated
irradiation with 40 Gy of X-rays (20 x 2 Gy/day). We also observed 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 through the
EGFR-SRC pathway. In general, our results demonstrate that cellular responses to ionizing
radiation in prostate cells depend on radiation quality and dose, and most importantly, on the
cell type (normal vs. cancer cells). The results obtained during this study will improve our
understanding of the biological mechanism(s) of prostate carcinogenesis and allow better
estimation of the cancer health risk following exposure to heavy ion radiation.
(This work is supported by NASA grant NNX10AC13G)