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Cell and Molecular Responses to ionizing Radiation in Normal tissues : Impact on Radiation Risk. Antone L. Brooks WSU-Tricities International Conference on July 13-14, 2007 Normal Tissue Radiation Effects Las Vegas, NV. acute exposure = all at once; chronic = hours, days, years.

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cell and molecular responses to ionizing radiation in normal tissues impact on radiation risk
Cell and Molecular Responses to ionizing Radiation in Normal tissues : Impact on Radiation Risk

Antone L. Brooks

WSU-Tricities

International Conference on July 13-14, 2007

Normal Tissue Radiation Effects Las Vegas, NV

slide2

acute exposure = all at once; chronic = hours, days, years

Ionizing Radiation

Dose Ranges

( Sievert )

Ionizing Radiation

Dose Ranges

( Sievert )

Cancer Radiotherapytotal dose to tumor

Cancer Radiotherapytotal dose to tumor

Whole body, acute: G-I destruction; lung damage; cognitive dysfunction

(death certain in 5 to 12 days)*

Whole body, acute: cerebral/ vascular breakdown (death in 0-5 days)*

0 10 20 30 40 50 60 70 80 90 100 Sv

0 10 20 30 40 50 60 70 80 90 100 Sv

Total Body Irradiation

(TBI) Therapy

Total Body Irradiation

(TBI) Therapy

Life Span Study (A-bomb survivor epidemiology)

Whole body, acute: circulating blood cell death; moderate G-I damage (death probable 2-3 wks)*

Acute Radiation Syndromes

Acute Radiation Syndromes

Whole body, acute: marked G-I and bone marrow damage (death probable in 1-2 wks)*

Solar flare dose on moon, no shielding

*Note: Whole body acute prognoses assume no medical intervention.)

0 1 2 3 4 5 6 7 8 9 10 Sv

0 1 2 3 4 5 6 7 8 9 10 Sv

Human LD50range, acute exposurewith medical intervention

Human LD50 range, acute exposure with no medical intervention (50% death in 3-6 weeks)*

Human LD50 range, acute exposure with no medical intervention (50% death in 3-6 weeks)*

Estimated dose for 3-yr Mars mission (current shielding)

Evidence for small increases in human cancer above 0.1 Sv acute exposures, 0.2 Sv chronic exposure

Cancer Epidemiology

Cancer Epidemiology

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Sv

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Sv

Typical mission doses on Intl. Space Station (ISS)

Medical Diagnostics, mSv

A- Chest x-ray (1 film) 0.1

B- Dental oral exam 1.6

C- Mammogram 2.5

D- Lumbosacral spine 3.2

E- PET 3.7

F- Bone (Tc-99m) 4.4

G- Cardiac (Tc-99m) 10

H- Cranial CT (MSAD) 50

(multiple scan average dose)

I- Barium contrast G-I 85

fluoroscopy (2 min scan)

J- Spiral CT- full body 30-100

Medical Diagnostics, mSv

A- Chest x-ray (1 film) 0.1

B- Dental oral exam 1.6

C- Mammogram 2.5

D- Lumbosacral spine 3.2

E- PET 3.7

F- Bone (Tc-99m) 4.4

G- Cardiac (Tc-99m) 10

H- Cranial CT (MSAD) 50

(multiple scan average dose)

I- Barium contrast G-I 85

fluoroscopy (2 min scan)

J- Spiral CT- full body 30-100

EPA guideline for lifesaving: 0.25 Sv

Natural bkg /yr Ramsar, Iran

DOE Low Dose Program

DOE Low Dose Program

EPA radiological emergency guideline for public relocation

H

H

I

I

J

J

“Storefront” full-body CT screening (one scan)

“Storefront” full-body CT screening (one scan)

0 10 20 30 40 50 60 70 80 90 100 mSv

0 10 20 30 40 50 60 70 80 90 100 mSv

DOE, NRC Dose Limit for Workers: 5 rem/yr = 50 mSv/yr

Natural bkg /yr

Kerala coast, India

DOE administrative control: 20 mSv/yr = 2 rem/yr

Medical Diagnostics (A-J)

Medical Diagnostics (A-J)

Typical annual doses for commercial airline flight crews

A

A

B

B

F

F

G

G

C

C

D

D

E

E

0 1 2 3 4 5 6 7 8 9 10 mSv

0 1 2 3 4 5 6 7 8 9 10 mSv

NRC cleanup criteria for site decommissioning / unrestricted use: 0.25 mSv/yr

Natural bkg /yr Yangjiang, China

Natural background,

U.S. average  3 mSv/yr

(includes radon)

Natural background,

U.S. average  3 mSv/yr

(includes radon)

Regulations & Guidelines

Regulations & Guidelines

Max releases DOE facilities

Round-trip

NY to London

LD50 = Lethal Dose to 50%

(the acute whole body dose that results in lethality to 50% of the exposed individuals)

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 mSv

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 mSv

EPA dose limit applicable to public drinking water systems: 0.04 mSv/yr

ANSI standard N43.17 Personnel scans max dose for total scans in 1 yr: 0.25 mSv

DOE, NRC Dose Limit for Public:

1 mSv/yr = 100 mrem/yr

(ICRP, NCRP)

EPA dose limit

from releases in air:

0.10 mSv/yr

Absorbed dose: 1 Gray = 100 rad

Dose equivalent: 1 Sievert = 100 rem

1 mSv = 100 mrem

(1 Sv = 1 Gy for x- and gamma-rays)

Note: This chart was constructed with the intention of providing a simple, user-friendly, “order-of-magnitude” reference for radiation quantities of interest to scientists, managers, and the general public. In that spirit, most quantities were expressed in the more commonly used radiation protection unit, the rem (or Sievert, 2nd page), and medical doses are not in “effective” dose. It is acknowledged that the decision to use one set of units does not address everyone’s needs. (NRC—US Nuclear Regulatory Commission; EPA—US Environmental Protection Agency) Disclaimer: Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information disclosed.

Chart compiled by NF Metting, Office of Science, DOE/BER “Orders of Magnitude” revised March 2006

Chart compiled by NF Metting, Office of Science, DOE/BER “Orders of Magnitude” revised March 2006

acute exposure = all at once; chronic = hours, days, years

Ionizing Radiation

Dose Ranges

( Sievert )

Cancer Radiotherapytotal dose to tumor

Whole body, acute: G-I destruction; lung damage; cognitive dysfunction

(death certain in 5 to 12 days)*

Whole body, acute: cerebral/ vascular breakdown (death in 0-5 days)*

0 10 20 30 40 50 60 70 80 90 100 Sv

Total Body Irradiation

(TBI) Therapy

Life Span Study (A-bomb survivor epidemiology)

Whole body, acute: circulating blood cell death; moderate G-I damage (death probable 2-3 wks)*

Acute Radiation Syndromes

Whole body, acute: marked G-I and bone marrow damage (death probable in 1-2 wks)*

Solar flare dose on moon, no shielding

*Note: Whole body acute prognoses assume no medical intervention.)

0 1 2 3 4 5 6 7 8 9 10 Sv

Human LD50range, acute exposurewith medical intervention

Human LD50 range, acute exposure with no medical intervention (50% death in 3-6 weeks)*

Estimated dose for 3-yr Mars mission (current shielding)

Evidence for small increases in human cancer above 0.1 Sv acute exposures, 0.2 Sv chronic exposure

Cancer Epidemiology

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Sv

Typical mission doses on Intl. Space Station (ISS)

Medical Diagnostics, mSv

A- Chest x-ray (1 film) 0.1

B- Dental oral exam 1.6

C- Mammogram 2.5

D- Lumbosacral spine 3.2

E- PET 3.7

F- Bone (Tc-99m) 4.4

G- Cardiac (Tc-99m) 10

H- Cranial CT (MSAD) 50

(multiple scan average dose)

I- Barium contrast G-I 85

fluoroscopy (2 min scan)

J- Spiral CT- full body 30-100

EPA guideline for lifesaving: 0.25 Sv

Natural bkg /yr Ramsar, Iran

DOE Low Dose Program

EPA radiological emergency guideline for public relocation

H

I

J

“Storefront” full-body CT screening (one scan)

0 10 20 30 40 50 60 70 80 90 100 mSv

DOE, NRC Dose Limit for Workers: 5 rem/yr = 50 mSv/yr

Natural bkg /yr

Kerala coast, India

DOE administrative control: 20 mSv/yr = 2 rem/yr

Medical Diagnostics (A-J)

Typical annual doses for commercial airline flight crews

A

B

F

G

C

D

E

0 1 2 3 4 5 6 7 8 9 10 mSv

NRC cleanup criteria for site decommissioning / unrestricted use: 0.25 mSv/yr

Natural bkg /yr Yangjiang, China

Natural background,

U.S. average  3 mSv/yr

(includes radon)

Regulations & Guidelines

Max releases DOE facilities

Round-trip

NY to London

LD50 = Lethal Dose to 50%

(the acute whole body dose that results in lethality to 50% of the exposed individuals)

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 mSv

EPA dose limit applicable to public drinking water systems: 0.04 mSv/yr

ANSI standard N43.17 Personnel scans max dose for total scans in 1 yr: 0.25 mSv

DOE, NRC Dose Limit for Public:

1 mSv/yr = 100 mrem/yr

(ICRP, NCRP)

EPA dose limit

from releases in air:

0.10 mSv/yr

Absorbed dose: 1 Gray = 100 rad

Dose equivalent: 1 Sievert = 100 rem

1 mSv = 100 mrem

(1 Sv = 1 Gy for x- and gamma-rays)

Note: This chart was constructed with the intention of providing a simple, user-friendly, “order-of-magnitude” reference for radiation quantities of interest to scientists, managers, and the general public. In that spirit, most quantities were expressed in the more commonly used radiation protection unit, the rem (or Sievert, 2nd page), and medical doses are not in “effective” dose. It is acknowledged that the decision to use one set of units does not address everyone’s needs. (NRC—US Nuclear Regulatory Commission; EPA—US Environmental Protection Agency) Disclaimer: Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information disclosed.

Chart compiled by NF Metting, Office of Science, DOE/BER “Orders of Magnitude” revised March 2006

cell and molecular responses to ionizing radiation in normal tissues impact on radiation risk3
Cell and Molecular Responses to ionizing Radiation in Normal tissues : Impact on Radiation Risk
  • Understand the differences in the mechanisms of action for low vs high doses of radiation
  • Evaluate the LNT hypothesis and the DDREF for low dose radiation exposure
  • To provide a scientific basis for radiation standards in the low dose region
  • Provide up-to-date information to researchers and public on low dose effects

http://www.lowdose.energy.gov

mechanistic studies
Mechanistic Studies
  • How can the research in the low dose region move from observations to mechanisms?
  • What is a mechanistic study?
    • New and more sensitive techniques to detect radiation induced changes?
    • New models?
    • Different application of data i.e. molecular epidemiology?
    • Systems biology?
  • Understanding the responses at the level that make it possible to predict and potentially modify the outcome of radiation exposure!!!
biological responses induced by low doses of radiation
Biological Responses Induced by Low Doses of Radiation

AdaptiveResponse

Genomic Instability

Bystander Effects

Genetic Sensitivity

radiation induced changes in gene expression adaptive and non adaptive cells
Radiation induced changes in gene expression: adaptive and non-adaptive cells

At 50 mGy Radiation Exposure

12,000 Genes

Non-adaptive Cells

All Cells

Adaptive Cells

57

47

45

Coleman et al 2005

adaptive vs non adaptive radiosensitive genes

50mGy

NA

A

A

Group 1

Genes up-regulated by radiation in all cells

Group 2

Genes down-regulated by radiation in all cells

Group 3

Genes up-regulated by radiation in adaptive cells, but down regulated in non-adaptive

Group 4

Genes down -regulated by radiation in adaptive cells, but up-regulated in non-adaptive

Adaptive vs non-adaptive radiosensitive genes
gene response
Gene Response

Adaptive

Non-Adaptive

vs

DNA Repair

Stress Response

Apoptosis

Cell Cycle

Coleman et al 2005

slide10

Low Dose-induced Apoptosis of Transformed Cells

Transformed cell

- O2:

- O2:

HO

Cl-

- O2:

- O2:

- O2:

PO

Cl-

Cl-

PO

- O2:

-NO

-NO

TGFβ

TGFβ

LTGFβ

LTGFβ

Non-transformed cell

Non-transformed bystander cell

OH-

APOPTOSIS

ONOO-

Cl-

Cl-

Georg Bauer

biological responses induced by low doses of radiation11
Biological Responses Induced by Low Doses of Radiation

AdaptiveResponse

Genomic Instability

Bystander Effects

Genetic Sensitivity

bystander effect all or none dose response
Bystander EffectAll-or-none dose response

Fraction of cells damaged

One cell targeted per dish

Four cells targeted per dish

Numbers of particles per targeted cell

Belyakov et al. 2001

calcium fluxes as bystander signals 24 h post irradiation with 5 alpha particles
Calcium fluxes as bystander signals (24 h post-irradiation with 5 alpha particles)

10 % cells

Nuclear 100 % cells

Cytoplasmic 100% cells

10% cells treated with DMSO

Control

Shao et al 2006

biological responses induced by low doses of radiation16
Biological Responses Induced by Low Doses of Radiation

AdaptiveResponse

Genomic Instability

Bystander Effects

Genetic Sensitivity

genomic instability is modified by adaptive response
Genomic instability is modified by adaptive response

GFP+/- Colonies

Genomic Instabiilty

1

2

3

10

1

2

3

10

Dose (cGy)

Huang et al. 2007

dose rate modification of radiation responses
Dose-rate modification of radiation responses
  • Molecular understanding of dose-rate effects
  • Tissue studies
  • Whole Animal Studies
  • What is the appropriate value of DDREF?
slide19
γH2AX

Ishizaki et al. 2004

it takes a tissue to make a tumor
It takes a tissue to make a tumor...

Normal mammary epithelial cells (milk production)

CANCER

Normal matrix

Artificial substrate

Mammary epithelial cells

Normal matrix

Irradiated matrix

CANCER

Barcellos-Hoff et al. 2000

a bomb experience

2.0

0.5

1. 0

1.5

A-Bomb Experience

LNT

High Dose

High Dose-Rate

5%/Sv increase in Cancer Mortality

35

DDREF

DOE Low Dose Radiation Research Program

%Cancer Mortality

30

LNT

Low Dose

Low Dose-Rate

25

23

? Background Cancer Mortality ?

0.1

Background Radiation in

70 years

Dose (Sv)

radiation induced cancer
Radiation-induced Cancer
  • Public Perception

Each and every ionization causes cancer.

(LNTH and BEIR VII)

  • Scientific Data

The risk for radiation induced cancer is small.

(LNTH and BEIR VII)

It takes very large amounts of radiation,

delivered to a large population,

to produce a detectable increasein cancer frequency.

effects of atomic bomb
Killed outright by the bomb or acute radiation effects.

Survived for lifespan study

More than 100,000 people

86,572 people

Effects of Atomic Bomb
a bomb survivor studies

5% less cancer than total controls

2.45 Km (5 mSv)

3 Km (2 mSv)

46,249 “Exposed”

5 Km

10,159 “Controls”

A-BOMB SURVIVOR STUDIES

Pierce and Preston 2000

a bomb survivor studies27
A-BOMB SURVIVOR STUDIES

Preston et al. 2004

3 Km

CONTROL AREA

2. Km

Excess

Excess

Solid Tumors

Leukemias

1 Km

113

116

99

41

44

2

28.2

27.7

18.9

10.4

4.7

4.0

0.1

64

572 Total Excess Cancers

479 Total

93 Total

atomic bomb survivor excess cancer
Atomic Bomb Survivor Excess Cancer

Population of Survivors Studied86,572

40% of these people are still alive 60 years after the bomb

Cancer Mortality observed after the Bomb 10,127

Cancers Mortality Expected without Bomb 9,555

Total Cancer Mortality Excess572

Excess Tumor 479

Excess Leukemia 94

+

=

572

slide31

acute exposure = all at once; chronic = hours, days, years

Ionizing Radiation

Dose Ranges

( Sievert )

Ionizing Radiation

Dose Ranges

( Sievert )

Cancer Radiotherapytotal dose to tumor

Cancer Radiotherapytotal dose to tumor

Whole body, acute: G-I destruction; lung damage; cognitive dysfunction

(death certain in 5 to 12 days)*

Whole body, acute: cerebral/ vascular breakdown (death in 0-5 days)*

0 10 20 30 40 50 60 70 80 90 100 Sv

0 10 20 30 40 50 60 70 80 90 100 Sv

Total Body Irradiation

(TBI) Therapy

Total Body Irradiation

(TBI) Therapy

Life Span Study (A-bomb survivor epidemiology)

Whole body, acute: circulating blood cell death; moderate G-I damage (death probable 2-3 wks)*

Acute Radiation Syndromes

Acute Radiation Syndromes

Whole body, acute: marked G-I and bone marrow damage (death probable in 1-2 wks)*

Solar flare dose on moon, no shielding

*Note: Whole body acute prognoses assume no medical intervention.)

0 1 2 3 4 5 6 7 8 9 10 Sv

0 1 2 3 4 5 6 7 8 9 10 Sv

Human LD50range, acute exposurewith medical intervention

Human LD50 range, acute exposure with no medical intervention (50% death in 3-6 weeks)*

Human LD50 range, acute exposure with no medical intervention (50% death in 3-6 weeks)*

Estimated dose for 3-yr Mars mission (current shielding)

Evidence for small increases in human cancer above 0.1 Sv acute exposures, 0.2 Sv chronic exposure

Cancer Epidemiology

Cancer Epidemiology

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Sv

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Sv

Typical mission doses on Intl. Space Station (ISS)

Medical Diagnostics, mSv

A- Chest x-ray (1 film) 0.1

B- Dental oral exam 1.6

C- Mammogram 2.5

D- Lumbosacral spine 3.2

E- PET 3.7

F- Bone (Tc-99m) 4.4

G- Cardiac (Tc-99m) 10

H- Cranial CT (MSAD) 50

(multiple scan average dose)

I- Barium contrast G-I 85

fluoroscopy (2 min scan)

J- Spiral CT- full body 30-100

Medical Diagnostics, mSv

A- Chest x-ray (1 film) 0.1

B- Dental oral exam 1.6

C- Mammogram 2.5

D- Lumbosacral spine 3.2

E- PET 3.7

F- Bone (Tc-99m) 4.4

G- Cardiac (Tc-99m) 10

H- Cranial CT (MSAD) 50

(multiple scan average dose)

I- Barium contrast G-I 85

fluoroscopy (2 min scan)

J- Spiral CT- full body 30-100

EPA guideline for lifesaving: 0.25 Sv

Natural bkg /yr Ramsar, Iran

DOE Low Dose Program

DOE Low Dose Program

EPA radiological emergency guideline for public relocation

H

H

I

I

J

J

“Storefront” full-body CT screening (one scan)

“Storefront” full-body CT screening (one scan)

0 10 20 30 40 50 60 70 80 90 100 mSv

0 10 20 30 40 50 60 70 80 90 100 mSv

DOE, NRC Dose Limit for Workers: 5 rem/yr = 50 mSv/yr

Natural bkg /yr

Kerala coast, India

DOE administrative control: 20 mSv/yr = 2 rem/yr

Medical Diagnostics (A-J)

Medical Diagnostics (A-J)

Typical annual doses for commercial airline flight crews

A

A

B

B

F

F

G

G

C

C

D

D

E

E

0 1 2 3 4 5 6 7 8 9 10 mSv

0 1 2 3 4 5 6 7 8 9 10 mSv

NRC cleanup criteria for site decommissioning / unrestricted use: 0.25 mSv/yr

Natural bkg /yr Yangjiang, China

Natural background,

U.S. average  3 mSv/yr

(includes radon)

Natural background,

U.S. average  3 mSv/yr

(includes radon)

Regulations & Guidelines

Regulations & Guidelines

Max releases DOE facilities

Round-trip

NY to London

LD50 = Lethal Dose to 50%

(the acute whole body dose that results in lethality to 50% of the exposed individuals)

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 mSv

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 mSv

EPA dose limit applicable to public drinking water systems: 0.04 mSv/yr

ANSI standard N43.17 Personnel scans max dose for total scans in 1 yr: 0.25 mSv

DOE, NRC Dose Limit for Public:

1 mSv/yr = 100 mrem/yr

(ICRP, NCRP)

EPA dose limit

from releases in air:

0.10 mSv/yr

Absorbed dose: 1 Gray = 100 rad

Dose equivalent: 1 Sievert = 100 rem

1 mSv = 100 mrem

(1 Sv = 1 Gy for x- and gamma-rays)

Note: This chart was constructed with the intention of providing a simple, user-friendly, “order-of-magnitude” reference for radiation quantities of interest to scientists, managers, and the general public. In that spirit, most quantities were expressed in the more commonly used radiation protection unit, the rem (or Sievert, 2nd page), and medical doses are not in “effective” dose. It is acknowledged that the decision to use one set of units does not address everyone’s needs. (NRC—US Nuclear Regulatory Commission; EPA—US Environmental Protection Agency) Disclaimer: Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information disclosed.

Chart compiled by NF Metting, Office of Science, DOE/BER “Orders of Magnitude” revised March 2006

Chart compiled by NF Metting, Office of Science, DOE/BER “Orders of Magnitude” revised March 2006

acute exposure = all at once; chronic = hours, days, years

Ionizing Radiation

Dose Ranges

( Sievert )

Cancer Radiotherapytotal dose to tumor

Whole body, acute: G-I destruction; lung damage; cognitive dysfunction

(death certain in 5 to 12 days)*

Whole body, acute: cerebral/ vascular breakdown (death in 0-5 days)*

0 10 20 30 40 50 60 70 80 90 100 Sv

Total Body Irradiation

(TBI) Therapy

Life Span Study (A-bomb survivor epidemiology)

Whole body, acute: circulating blood cell death; moderate G-I damage (death probable 2-3 wks)*

Acute Radiation Syndromes

Whole body, acute: marked G-I and bone marrow damage (death probable in 1-2 wks)*

Solar flare dose on moon, no shielding

*Note: Whole body acute prognoses assume no medical intervention.)

0 1 2 3 4 5 6 7 8 9 10 Sv

Human LD50range, acute exposurewith medical intervention

Human LD50 range, acute exposure with no medical intervention (50% death in 3-6 weeks)*

Estimated dose for 3-yr Mars mission (current shielding)

Evidence for small increases in human cancer above 0.1 Sv acute exposures, 0.2 Sv chronic exposure

Cancer Epidemiology

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Sv

Typical mission doses on Intl. Space Station (ISS)

Medical Diagnostics, mSv

A- Chest x-ray (1 film) 0.1

B- Dental oral exam 1.6

C- Mammogram 2.5

D- Lumbosacral spine 3.2

E- PET 3.7

F- Bone (Tc-99m) 4.4

G- Cardiac (Tc-99m) 10

H- Cranial CT (MSAD) 50

(multiple scan average dose)

I- Barium contrast G-I 85

fluoroscopy (2 min scan)

J- Spiral CT- full body 30-100

EPA guideline for lifesaving: 0.25 Sv

Natural bkg /yr Ramsar, Iran

DOE Low Dose Program

EPA radiological emergency guideline for public relocation

H

I

J

“Storefront” full-body CT screening (one scan)

0 10 20 30 40 50 60 70 80 90 100 mSv

DOE, NRC Dose Limit for Workers: 5 rem/yr = 50 mSv/yr

Natural bkg /yr

Kerala coast, India

DOE administrative control: 20 mSv/yr = 2 rem/yr

Medical Diagnostics (A-J)

Typical annual doses for commercial airline flight crews

A

B

F

G

C

D

E

0 1 2 3 4 5 6 7 8 9 10 mSv

NRC cleanup criteria for site decommissioning / unrestricted use: 0.25 mSv/yr

Natural bkg /yr Yangjiang, China

Natural background,

U.S. average  3 mSv/yr

(includes radon)

Regulations & Guidelines

Max releases DOE facilities

Round-trip

NY to London

LD50 = Lethal Dose to 50%

(the acute whole body dose that results in lethality to 50% of the exposed individuals)

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 mSv

EPA dose limit applicable to public drinking water systems: 0.04 mSv/yr

ANSI standard N43.17 Personnel scans max dose for total scans in 1 yr: 0.25 mSv

DOE, NRC Dose Limit for Public:

1 mSv/yr = 100 mrem/yr

(ICRP, NCRP)

EPA dose limit

from releases in air:

0.10 mSv/yr

Absorbed dose: 1 Gray = 100 rad

Dose equivalent: 1 Sievert = 100 rem

1 mSv = 100 mrem

(1 Sv = 1 Gy for x- and gamma-rays)

Note: This chart was constructed with the intention of providing a simple, user-friendly, “order-of-magnitude” reference for radiation quantities of interest to scientists, managers, and the general public. In that spirit, most quantities were expressed in the more commonly used radiation protection unit, the rem (or Sievert, 2nd page), and medical doses are not in “effective” dose. It is acknowledged that the decision to use one set of units does not address everyone’s needs. (NRC—US Nuclear Regulatory Commission; EPA—US Environmental Protection Agency) Disclaimer: Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information disclosed.

Chart compiled by NF Metting, Office of Science, DOE/BER “Orders of Magnitude” revised March 2006

medical radiation exposures
Medical Radiation Exposures
  • 200 million medical x-rays/year
    • X-ray 0.1 mGy
  • 100 million dental x-rays/year
    • Dental 0.06 mGy
  • 10 million doses of radiopharmaceuticals/yr
  • 67 million CT scans/year
    • Head scan 4-6 mGy/scan
    • Body scan 40-100 mGy/scan
  • Large doses from radiation therapy
lnth assumption with dose
LNTH Assumption with Dose

Low dose x large number of subjects

High dose x small number of subjects

Energy to system

impact on dose response
Impact on Dose-response
  • Production of damage
  • Linear processes
    • Deposition of energy
    • DNA damage
  • Processing of damage
  • Non-linear processes
    • Induction of Apoptosis
    • Gene & Protein expression

Physics

Biology

Balancing Act

linking cellular events to cancer
Linking Cellular Events to Cancer

CANCER RESISTANT

SENSITIVE TO CANCER

low dose radiation responses old paradigm

Energy deposited in the nucleus

Ionizations produced

DNA broken

Mutations

Chromosomal Aberrations

Cell Death

Cell Transformation

CANCER

Low Dose Radiation Responses(Old Paradigm)
low dose radiation responses new paradigm

GENETIC SENSITIVITY

AdaptiveResponse

DNA may be broken, or other molecules may be damaged

Genomic Instability

Bystander Effects

Apoptosis (Selective)

Cell Killing

Micronuclei

Mutations

Low Dose Radiation Responses(New Paradigm)

Energy deposited in the nucleus OR cytoplasm

Ionizations produced

Epigenetic factors

Apoptotic DNA fragmentation factor

Other Proteins

PCNA,

RPA

and APE

TISSUE RESPONSE

Triggers biological processes

CANCER?

Oxidative Status

Upregulation of antioxidant enzymes

Inhibition of superoxide anions

SIGNALING

Direct Cell-cell

Indirect –secretive

Signaling molecules

++Ca DNA-PKc’s TGF-B

Modifies GENE AND PROTEIN EXPRESSIOn

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Accomplishments:

DOE Low Dose Radiation Research Program

  • Effectively integrated advances in biological and physical technology to define low dose radiation effects (0.10 Gy or less) which provides a strong scientific basis for radiation standards.
  • Characterized unique responses that exist after low dose radiation exposure (bystander effects, adaptive response and genomic instability) that can influence the shape of the dose-response at low doses
  • Defined the unique signaling molecules induced by low doses of radiation
  • Integrated studies on low-dose-hypersensitivity, apoptosis, gene expression, protein expression, and molecular pathways to help define the mechanisms of action for low dose responses
  • Determined that low doses of radiation changes the reactive oxygen status of the cell and influence radiation-induced phenotypic changes
  • Linked cellular and molecular changes to low dose phenotypic changes and determined how these changes influence cancer risk
  • Defined the role of complex tissue interaction in modification of cancer response following low dose radiation exposure
  • Recognized and studied the importance of genetic resistance and sensitivity on low dose radiation response

2. Emphasized research on the cellular and molecular mechanisms of action associated with low and high does of radiation to differentiate between these responses

3. The research has resulted in the need for changes in radiation paradigms and challenged models used to extrapolate the cancer and genetic risk from high to low radiation.

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