chronic radiation exposure induces cellular adaptive...

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: glrusso@isa.cnr.ithttp://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 …….. !!!