Extended investigations of low dose radiation effects

  • Schöllnberger, Helmut, (Projektleitung)
  • Hofmann, Werner (Projektmitarbeiter/in)

Projektdetails

Beschreibung

This 3-year project is an extension of Dr. Schöllnberger’s ongoing research efforts. The project is also in the tradition of his earlier high-level studies in the US and the Netherlands (EU Marie Curie Individual Fellowship). One important biological endpoint that has been extensively used in the past for risk estimations is in vitro neoplastic transformation. In the planned project a novel biophysical model will be developed that allows to simulate this endpoint. The model is especially suited to describe protective effects of low doses of low-LET radiation as discovered by Azzam et al. They observed that after low dose gamma-ray exposures the transformation frequency (TF) was reduced from the spontaneous level to a rate three- to fourfold below that level. In the new project different biological mechanisms that could lead to these protective effects will be studied. One possibility is bystander-induced apoptosis. Genomic instability will also be included into the model together with low-dose Hyperradiosensitivity and Induced Radioresistance. The new models will be tested on representative data sets of Dr. Redpath’s laboratory that shows a reduction of the TF below the spontaneous level. Other possibilities to explain the data sets of Azzam and Redpath relate to a radiological induction of radical scavengers and error-free DNA repair that also impact on endogenously produced radicals and DNA lesions. This will also be investigated. These deterministic models will be made stochastic by Monte Carlo Simulations. The project can lead to improved and more realistic risk estimates for low doses of ionizing radiations. With respect to the nuclear power stations at its borders, the planned project is especially relevant for Austrian citizens.

The system-biological approach encompasses a more comprehensive biophysical model than those that have been used so far for the assessment of biological effects of low dose irradiation. The proposed model comprises endogenous DNA lesions together with radiation-induced lesions and various inducible cellular defence mechanisms that can impact on the endogenous and the radiation-induced lesions. The model can be used in a deterministic and stochastic version (via Monte Carlo simulations). With this approach, two levels of biological organization are described: the molecular and the cellular level. Dr. Schöllnberger’s existing cancer models will be used during the planned project to perform forward simulations using key findings of the planned model fits to in vitro data.

The 3-year project directly addresses the low dose controversy, with LNT advocates who strongly rely on analyses of epidemiological data on one side, and on the other side those who have put forward ideas of how the above mentioned nonlinear low dose mechanisms might lead to protective effects at low doses. Like only a few other investigators, the applicant integrates lowdose inducible biological mechanisms together with endogenous DNA lesions into state-of-the-art deterministic and stochastic models for in vitro neoplastic transformation. The models that are to be developed pose an important step toward a comprehensive model that includes all biological mechanisms that are essential for the biological outcome of low dose exposures.
AkronymLow Dose II
StatusAbgeschlossen
Tatsächlicher Beginn/ -es Ende1/07/0930/09/10

Systematik der Wissenschaftszweige 2002

  • 1449 Strahlenbiologie
  • 1207 Biophysik