Split-dose exposures versus dual ion exposure in human cell neoplastic transformation |
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Authors: | Paula V Bennett Noelle C Cutter Betsy M Sutherland |
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Institution: | (1) Biology Department, Bldg 463, Brookhaven National Laboratory, Upton, NY 11973-5000, USA;(2) Present address: Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794-5222, USA |
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Abstract: | Since radiation fields of space contain many-fold more protons than high atomic number, high energy (HZE) particles, cells
in astronaut crews will experience on average several proton hits before an HZE hit. Thus radiation regimes of proton exposure
before HZE particle exposure simulate space radiation exposure, and measurement of the frequency of neoplastic transformation
of human primary cells to anchorage-independent growth simulates an initial step in cancer induction. Although previous investigations
indicated a synergistic increase in transformation yields in the cells exposed to protons followed by HZE particles, these
experiments did not differentiate between the effect of splitting of the dose into two fractions and that of changing the
ion beams. To test this, we irradiated cells with split doses of either protons or HZE particles, then measured clonogenic
survival and neoplastic transformation, as measured by colony formation in semi-solid soft agar medium. The data show that
the split dose of 20 cGy plus 20 cGy of either H or HZE ions gave about the same effect as the 40 cGy uninterrupted dose,
quite different from the effect of the mixed ion beam H + HZE irradiation. We also asked if lower proton doses than 20 cGy
followed 15 min later by 20 cGy of HZE ions gave greater than additive transformation frequencies. Substantial increases in
transformation levels were observed for all proton doses tested, including 1 cGy. These results point to the signal importance
of protons in affecting the effect of space radiation on human cells. |
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