The Cosmic Silence Experiment

1. The Cosmic Silence Experiment Junior Grants F. Antonelli, C. Carbone, M. Pinto Massimo Pinto Rome, November 26th 2007

2. What is it? A unique experiment on the biological effects of background environmental radiation on living human cells

3. Rationale Before Cosmic Silence Cosmic Silence experimental model Re sults Developments Presentation Sequence

4. Rationale Biological responses to low doses of ionizing radiation look more complex than originally thought. Once DNA damage-centred... Ionising radiation • Now broadened to include non (DNA)-targeted effects: • Bystander effects • Genomic Instability • Adaptive Responses

5. Adaptive Responses conditioning dose challenge dose + Effect

6. Adaptive Responses - II Cronic conditioning with 3H β-particles challenge dose + Effect Olivieri, Bodycote and Wolff Science, 1984

7. Radiation is everywhere Cosmic Inhaled Radon Bodies Plants Radioactive Elements Rocks Adapted from:

8. Background Radiation Most background radiation is natural.It has always been here.People have always lived with it. In fact, the body has developed repair mechanisms to deal with negative effects of background radiation Adapted from:

9. What if background radiation was significantly reduced? Would living organisms lose their adaptation? Would we be less prepared to an insult of ionizing radiation? Rationale

10. 0 2 4 6 8 10 Is background radiation a conditioning agent? Two laboratories for two different background radiation levels Gran Sasso d’Italia Roma Teramo 1400 m km INFN Lab ISS Rome INFN-LNGS

11. In vitro dosimetry Cosmic n, p g(Earth) g (Earth and cosmic) 222Rn 222Rn 240 µGy/month 3 µGy/month 1 Gy = 1 Joule / kg

12. Our past results Yeast (S. Cerevisiae), 1995 Chinese Hamster cells, 2002

13. Chinese hamster cells 3 months 9 months Low background Rome t0

14. So, good news for all Yeast cells and Chinese Hamsters in the audience. But please, don’t go live inside any mountain.

15. Working hypothesis Natural background environmental radiation can adapt human cells in vitro to acute doses of ionizing radiation

16. Cosmic Silence Experiment 1995 2002 • Immortalised - goes on for long times • 2 independent genetic loci for mutation experiments for two functionally distinct DNA repair mechanisms • Frequent criopreservations in LN2 • Everything rigorously identical The Human lymphoblastoid line TK6

17. Culture Monitoring 2006 2007 2006 2007

18. DNA damage Micronuclei induction Parallel gene expression analysis Apoptosis “Reactive Oxygen Species” (ROS) Measurements – Year 1

19. 300 250 Micronuclei frequency 200 + + 150 100 50 0 DNA damage, 6 mo. = 2 Gy

20. Cancer Risk A-Bomb survivors and nuclear industry workers, epidemiological data Excess cancer risk from radiatoin Cosmic silence experiment LNT model extrapolation to low doses Radiation Dose (Gy) or dose rate

21. Coming up next • Human cells – LNGS cells back to Rome after 12 months. Searching for re-adaptation • in vivo systems such as C. Elegans are being considered

22. Massimo P. Francesca A. Cristina C.