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Chronic Radiation Exposure Induces Cellular Adaptive Response in Interventional Cardiologists
Gian Luigi Russo
“DOSE-RESPONSE 2012”The 11th Annual International Conference
April 25, 2012University of Massachusetts, Amherst, MA
Istituto di Scienze dell'Alimentazionevia Roma 64, 83100 Avellino
e-mail: [email protected]://www.isa.cnr.it
Gian Luigi Russo Amherst, MA 04/25/2012
“Friendly fire” on Interventional Cardiologists
0InterventionalCardiologist
Orthopedists Nuclear Physicians
Radiologists
Chest x
‐rays p
er head/pe
r year
300(6 mSv)
250(5 mSv)
200(4 mSv)
150(3 mSv)
100(2 mSv)
50(1 mSv)
Vano E et al, BJR 1998
“Exposure of interventional radiologists is above and beyond every regulatory support” (DIMOND EU Conc Action, 2001: Professional ICRP limit: 20 mSv/year )
“Lifetime extra‐cancer risk of interventional cardiologists and electrophysiologists: 1 in 100‐1 in 250 (100‐200 mSv) after 11‐25 years of cath lab” (Venneri L. et al, Am Heart J 2009)
“Not infrequently, there is a machismo disregard for radiation protection”
Rita Watson, Sayonara ALARA, Cath Cardiov Diagn, 1997
Gian Luigi Russo Amherst, MA 04/25/2012
DNA Damage in Interventional Cardiologists
Andreassi et al, FASEB J 2005
Gian Luigi Russo Amherst, MA 04/25/2012
DNA Damage in Interventional Cardiologists
Gian Luigi Russo Amherst, MA 04/25/2012
Dose
Canc
er F
requ
ency
LNTHLinear
Background Cancer Rate
Data and radiation-induced cancer
No data
Threshold
Adaptive response
Radiation Dose-Response Models
Gian Luigi Russo Amherst, MA 04/25/2012
“LDR generate risk factors that are lower than predicted by the LNT, that these risks do not exist, or even that low doses of radiation may even be beneficial (linear model with a threshold)”
Gene Response
DNA Repair Stress Response Apoptosis Cell Cycle
Coleman et al 2005
vs
Gian Luigi Russo Amherst, MA 04/25/2012
Study Design
Oxidative stress markersApoptotic markers
10 UNEXPOSED SUBJECTS
Gian Luigi Russo Amherst, MA 04/25/2012
10 EXPOSED CARDIOLOGISTS
Characteristics of the Examinees
Gian Luigi Russo Amherst, MA 04/25/2012
Oxidative Stress in non-Exposed vs Exposed
Antioxidant Power in Serum
AN
TIO
XID
AN
T P
OW
ER
(Asc
orbi
c A
cid
Eq [µM
]
Gian Luigi Russo Amherst, MA 04/25/2012
H2O2SOD
OH-
Fe2+ MetalChelators
Oxidative damageDNALipidsProteins
ROO• RO•
O2-
2H+ + 2O2- → H2O2 + O2
ROS
SOD in non-Exposed vs Exposed
Klucinski et al., 2008
H2O2SOD
OH-
Fe2+ MetalChelators
Oxidative damageDNALipidsProteins
ROO• RO•
O2-
2H+ + 2O2- → H2O2 + O2
ROS H2O + O2catalase
2H2O2 → O2 + 2H2O
SOD in non-Exposed vs Exposed
Gian Luigi Russo Amherst, MA 04/25/2012
H2O2SOD
OH-
Fe2+ MetalChelators
ROO• RO•
O2-
2H+ + 2O2- → H2O2 + O2
ROS H2O + O2catalase
2H2O2 → O2 + 2H2O
GSRedglutathione reductase
NADPH
NADP+cellular energy
GSH(reduced)
GSSG(oxidized)
GPxglutathione peroxidase
2H2O 2
GSH in Erythrocytes of non-Exposed vsExposed
lipid hydroperoxides
DetoxificationGSH peroxidase (GPx)GSH transferase (GST)
GSH in Erythrocytes of non-Exposed vsExposed
Gian Luigi Russo Amherst, MA 04/25/2012
ROS in Erythrocytes of non-Exposed vsExposed
Gian Luigi Russo Amherst, MA 04/25/2012
Conclusion - 1
Gian Luigi Russo Amherst, MA 04/25/2012
Apoptotic Response in Interventional Cardiologist s
Louagie et al., Cell Biol Int. 1999; 23:611-7
Gian Luigi Russo Amherst, MA 04/25/2012
Conclusion - 2
Gian Luigi Russo Amherst, MA 04/25/2012
In interventional cardiologist chronic exposure to LDR induces at leasttwo physiological adaptive responses: enhanced antioxidant defence(GSH levels), increased baseline level of caspase-3 activity .
The biochemical remodelling induced by chronic LDR exposure ininterventional cardiologists might even overturn into a survivaladvantage
The biochemical remodelling induced by chronic LDR exposure mightcontribute to generate new guidelines in interventional cardiology, whichare currently based, almost exclusively, on minimizing radiation exposureby implementing safety measures and protection devices.
Overall Conclusions - 1
Dietary antioxidants may confer radioprotection.
Healthy Cath LabSTUDY
Funding:
Future Studies
Invasive cardiologists today have a unique opportunity to clarify the effects of chronic LDR.This large study is being conducted in Italy to address this question.It is done by interventional cardiologists on interventional cardiologists and for interventional cardiologistsThe aim is to clarify the cancer and non-cancer effects of chronic low dose radiation exposure
Gian Luigi RussoIdoloTedescoMaria Russo
Acknowledgments -1
Maria Grazia AndreassiEugenio Picano
Gaetano MottolaAngelo CioppaEugenio Picano
ISA-CNR IFC-CNR
Gian Luigi Russo Amherst, MA 04/25/2012
IdoloTedescoMaria RussoCarmela SpagnuoloRoberta IannittiAnnunziata Nappo
Acknowledgments -2
ISA-CNR
….Let’s hope not …….. !!!