Staff

Verwanger Thomas Dr., assistant (Thomas.VerwangerATsbg.ac.at)

Description

Molecular mechanisms of radon therapy

Cell protection against ROS by pre-treatment with low-dose alpha-irradiation

Low dose alpha irradiation (0.01 – 1 Gy with Am 241) can stimulate cell proliferation, as demonstrated by N. Strobl in her master thesis with SKIN (fibroblasts) and HaCaT cells (keratinocytes with p53 deficiency). Preliminary cell cycle measurements did not show an acceleration of the G1 or G2 phases.
As also found in the same study, radiation damage moderately increases until 1 Gy in BPH-1 (epithelial cells) and HaCaT; at 3 Gy, moderate recovery could be observed in the survival curves of all three cell lines at least 24 h pI (post-irradiation). Specific active repair mechanisms seem to be started or induced, which could be a de novo expression of protective genes.

The dose of about 1 Gy seems to have a specific effect on cells. Pro-inflammatory cytokines were up-regulated by irradiation with 1 Gy at 4 h pI. A G2-phase arrest was observed between 0.1 and 1 Gy, which points to repair activities, probably different from the recovery above. ROS formation in SKIN cells was reduced compared to the control only at 1 Gy. In contrast to the latter, DNA damage and lipid peroxidation was found in HaCaT cells at 1 Gy (Master thesis Strobl).
Molecular mechanisms of radon therapy

Cell protection against ROS by pre-treatment with low-dose alpha-irradiation

Low dose alpha irradiation (0.01 – 1 Gy with Am 241) can stimulate cell proliferation, as demonstrated by N. Strobl in her master thesis with SKIN (fibroblasts) and HaCaT cells (keratinocytes with p53 deficiency). Preliminary cell cycle measurements did not show an acceleration of the G1 or G2 phases.
As also found in the same study, radiation damage moderately increases until 1 Gy in BPH-1 (epithelial cells) and HaCaT; at 3 Gy, moderate recovery could be observed in the survival curves of all three cell lines at least 24 h pI (post-irradiation). Specific active repair mechanisms seem to be started or induced, which could be a de novo expression of protective genes.

The dose of about 1 Gy seems to have a specific effect on cells. Pro-inflammatory cytokines were up-regulated by irradiation with 1 Gy at 4 h pI. A G2-phase arrest was observed between 0.1 and 1 Gy, which points to repair activities, probably different from the recovery above. ROS formation in SKIN cells was reduced compared to the control only at 1 Gy. In contrast to the latter, DNA damage and lipid peroxidation was found in HaCaT cells at 1 Gy (Master thesis Strobl).

Since  apoptotic cell death occured at 1 Gy only in HaCaT cells,  p53 seems to be responsible for repair of lethal damage as well as DNA damage in the two other cell lines. Both could be connected. Inhibition of DNA synthesis, cell cycle arrest correlated with p53 signaling was also found by Chauhan V. et al. (1) after alpha-irradiation up to 0.9 Gy.
Similarly, a protection against lung cancer induction by alpha-irradiation was shown to be provided by stimulation with low-dose-gamma-radiation and to be connected with p53 activity (2). The reason could be epigenetic reprogramming of adaptive-response genes (3). However in these studies chronic low-rate gamma radiation protected against the transforming effects of alpha-irradiation.

Therefore, doses about 1 Gy (from 0.1 – 3 Gy) seem to stimulate several, probably different repair mechanisms, depending on the cell line. This is confirmed by Chauhan et al. (4), which found increased histone modifications (indicator for DNA damage) up to 1 Gy with Am 241, but no further increase until 2 Gy.

Aim

The aim of the study is therefore to investigate whether pre-treatment with low-dose alpha-irradiation protects against ROS damage in the cytoplasm.

References

1. Effects of alpha particle radiation on gene expression in human pulmonary epithelial cells. Chauhan V, Howland M, Mendenhall A, O´Hara S, Stocki TJ, McNamee JP, Wilkins RC.Int J Hyg Environ Health.      2012 Sep;215(5):522-35. Epub 2012 May 17.
2. Low-dose-radiation stimulated natural chemical and biological protection against lung cancer. Scott BR. Dose Response. 2008;6(3):299-318. Epub 2008 Mar 20.
3. Radiation-stimulated epigenetic reprogramming of adaptive-response genes in the lung: an evolutionary gift for mounting adaptive protection against lung cancer. Scott BR, Belinsky SA, Leng S, Lin Y, Wilder JA, Damiani LA. Dose Response. 2009 Jun 11;7(2):104-31.
4. Biological effects of alpha particle radiation exposure on human monocytic cells.Chauhan V, Howland M, Kutzner B, McNamee JP, Bellier PV, Wilkins RC. Int J Hyg Environ Health. 2012 Apr;215(3):339-44.

Project Funding

This project is partly funded by the Research Insitute Gastein – Paracelsus Medical University, Salzburg.