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Transcript of SECONDA CONFERENZA DEI PROGETTI DEL CENTRO FERMI 19-20 APRILE 2012 SALONE DELLE CONFERENZE DEL...
SECONDA CONFERENZA DEI PROGETTI DEL CENTRO FERMI
19-20 APRILE 2012
SALONE DELLE CONFERENZE DEL MINISTERO DELL’INTERNOROMA, PIAZZA DEL VIMINALE 1
In vitro-In vivo MUrine coSmiC siLEnce
experiment (MUSCLE)
D. Capece and E. Fratini (Centro Fermi)
on behalf of the Cosmic Silence Collaboration
Aim of MUSCLE Project
To understand the biological effects of environmental radiation
Peculiar low dose radiation effects (<100mGy)
Phenomenon in which unirradiated cells exhibit irradiated effects as a result of signals received from nearby irradiated cells.
Bystander effect
Genomic instability
Phenomenon characterized by an increase in the genetic spontaneous alteration observed in cells which have not themselves been irradiated, but are the progeny of an irradiated cell.
Peculiar low dose radiation effects (<100mGy)
Conditioning Dose Challenge Dose
Dam
ag
e +
Peculiar low dose radiation effects (<100mGy)
Adaptive reponse
Phenomenon that occurs when a low dose of mutagenic agent can protect from the biological damage of a subsequent high dose of the same or different mutagenica agents
Our Hypothesis
Life has evolved on Earth for 3 bilion years in the presence of
environmental ionizing radiation. All organism have therefore
incorporated in their normal biology a daily stiimulus of ultra-low-
dose environmental radiation that might act as conditioning agent.
LNGS – The Gran Sasso underground laboratory
Past Experiments
S. Cerevisiae cells
Chinese Hamster cells
Human cells
Satta et al., 1995.
Satta et al., 2002.Antonelli et al., 2008.
Carbone et al., 2009.Carbone & Pinto et al., 2010.
S. Cerevisiae D7 cells
Satta et al., Mutat. Res. 1995.
Chinese Hamster V79
Satta et al., Radiat. Environ. Biophys 2002.
Antonelli et al., Nuovo Cimento B 2008.
TK6 Lymphoblastoid cells
Carbone et al., Radiat. Environ. Biophys 2009.
Carbone & Pinto et al., Nuovo Cimento B 2010.
…Summarizing…
Compatible with our hypothesis of environmental radiation as a
conditioning agent, reduced environmental radiation conditions seem
to render cells, after several months of protracted culture:
Less tolerant to radiation-induced DNA damage
Less efficient in scavenging reactive oxygen species
pKZ1 Mouse Model
An ideal model for studying responses to very low doses of DNA
damaging agents
Matsuoka et al., Science 1991
LacZ Expression
Matsuoka et. al., Science 1991
pKZ1 Chromosomal Inversion Assay
P
P
DNA Inversion
ZcaL
LacZ
Experimental design
A11 Hybridoma cell line obtained from pKZ1 a splenocyte
Immortalized cell lines from brain and skin of neonatal pKZ1 mice
To use pKZ1 mouse chromosomal inversion assay to study
biological effects of environmental background radiation
Day et al., Radiat. Res. 1991
Experimental design
Istituto Superiore di Sanità Rome
LNGS - INFN
Reference environmental radiation (~ 2mGy/year)
Reduced environmental radiation (~ 25mGy/year)
Environmental Radiation
Compnents
ISS (External/Referenc
e Laboratory)
LNGS (Underground Laboratory)
Cosmic Rays 30 nGy/h Negligible
Cosmic and terrestrial g-rays
300 nGy/h 3.6 nGy/h
222Rn 1.7 nGy/h 0.17 nGy/h
Total dose rate ~ 330 nGy/h ~ 3.8 nGy/h
Experimental design
Rome Teramo
Inversion frequency
Doubling Time
Rate of apoptosis/autophagy
Redox cellular state
Biological End-points
ISS – Reference Environmental Radiation
LNGS – Reduced Environmental Radiation
Reference Environmental Radiation L’Aquila University
Reduced Environmental RadiationLNGS (L’Aquila)/LSC-Canfranc
underground laboratory (Saragozza)?
pKZ1 pKZ1
Perspectives
What happens in vivo?
INFNL. Satta
Istituto Superiore di SanitàG. Simone, M.A. Tabocchini
L’Aquila UniversityF. Zazzeroni, E. AlesseENEA Casaccia
R. Amendola
INFN-LNGSM. Balata
ENEAR. Amendola
Flinders University, AdelaideP. Sykes
Cosmic Silence Collaboration
CENTRO FERMID. Capece, E. Fratini, M.C. Carbone, M.
Pinto