Maslowski, Amy Jesse (2007-08). Low dose radiation interations with the transformation growth factor (TGF)-beta pathway. Doctoral Dissertation. Thesis uri icon

abstract

  • A major limiting factor for long-term, deep-space missions is the radiation dose to astronauts. Because the dose to the astronauts is a mixed field of low- and high-LET radiation, there is a need to understand the effects of both radiation types on whole tissue; however, there are limited published data on the effects of high-LET (linearenergy- transfer) radiation on tissue. Thus, we designed a perfusion chamber system for rat trachea in order to mimic in vivo respiratory tissue. We successfully maintained the perfused tracheal tissue ex vivo in a healthy and viable condition for up to three days. In addition, this project studied the effects of high-LET Fe particles on the overall transformation growth factor (TGF)-beta response after TGF-beta inactivation and compared the results to the TGF-beta response post x-ray irradiation. It was found that a TGF-beta response could be measured in the perfused tracheal tissue, for x-ray and Fe particle irradiations, despite the high autofluorescent background intrinsic to tissue. However, after comparing the TGF-beta response of x-ray irradiation to High-Z-Highenergy (HZE) irradiation, there was not a significant difference in radiation types. The TGF-beta response in x-ray and HZE irradiated perfusion chambers was also measured over time post irradiation. It was found that for 6 hour and 8 hour post irradiation, the TGF-beta response was higher for lower doses of radiation than for higher doses. This is in contrast to the 0 hour fixation which found the TGF-beta response to increase with increased dose. The inverse relationship found for 6 hour and 8 hour fixation times may indicate a threshold response for TGF-beta response; i.e., for low doses, a threshold of dose must be reached for an immediate TGF-beta response, otherwise the tissue responds more slowly to the irradiation damage. This result was unexpected and will require further investigation to determine if the threshold can be determined for the 250 kVp x-rays and 1 Gev Fe particles.
  • A major limiting factor for long-term, deep-space missions is the radiation dose to
    astronauts. Because the dose to the astronauts is a mixed field of low- and high-LET
    radiation, there is a need to understand the effects of both radiation types on whole
    tissue; however, there are limited published data on the effects of high-LET (linearenergy-
    transfer) radiation on tissue. Thus, we designed a perfusion chamber system for
    rat trachea in order to mimic in vivo respiratory tissue. We successfully maintained the
    perfused tracheal tissue ex vivo in a healthy and viable condition for up to three days. In
    addition, this project studied the effects of high-LET Fe particles on the overall
    transformation growth factor (TGF)-beta response after TGF-beta inactivation and
    compared the results to the TGF-beta response post x-ray irradiation. It was found that a
    TGF-beta response could be measured in the perfused tracheal tissue, for x-ray and Fe
    particle irradiations, despite the high autofluorescent background intrinsic to tissue.
    However, after comparing the TGF-beta response of x-ray irradiation to High-Z-Highenergy
    (HZE) irradiation, there was not a significant difference in radiation types. The
    TGF-beta response in x-ray and HZE irradiated perfusion chambers was also measured
    over time post irradiation. It was found that for 6 hour and 8 hour post irradiation, the TGF-beta response was higher for lower doses of radiation than for higher doses. This is
    in contrast to the 0 hour fixation which found the TGF-beta response to increase with
    increased dose. The inverse relationship found for 6 hour and 8 hour fixation times may
    indicate a threshold response for TGF-beta response; i.e., for low doses, a threshold of
    dose must be reached for an immediate TGF-beta response, otherwise the tissue
    responds more slowly to the irradiation damage. This result was unexpected and will
    require further investigation to determine if the threshold can be determined for the 250
    kVp x-rays and 1 Gev Fe particles.

publication date

  • August 2007