Timing of onset of symptoms c orrelates with the lifespan of the function al cells .
Early Effects: stem cells are the “target”
Effects occur in a few days to weeks
Rapidly dividing cell populations
Exam ples: skin epiderm i s, gastrointestinal tract, hematopoietic system
Damage can be repaired. Stem cells repopulate rapidly.
La te Effe c t s:
Effects occur in m onths to years.
Slowly proliferating tissues : lung, kidney, liver, CNS
Damage never repaired com p letely
Vascular damage or mature f unctional cells as the “target”?
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Chroni c eff e cts of radiati o n exp o su re
Cells not killed, but damaged…..
Cataract formation
Genetic (hereditary) effects
Effects on the fetus
Carcinogenic effect s (cancer)
Human Radiation Exposure Data
Japanese A-bomb survivors
93,000 survivors
27,000 non-exposed com p arable individuals as controls
Location at the tim e of the blast m u st be accounted for in the dosim etry.
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[Image removed due to copyright considerations]
RERF: Radiation Effects Res earch Foundation
Joint US-Japan research founda tion following all of the survivors for life.
Hereditary Effects: effects on the offspring
Radiation does not produce “new mutations”.
Radiation increases the incidence of mutati ons that occur spontaneously in the population.
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[Image removed due to copyright considerations]
Doubling dose : increases the natural background frequency by a factor of 2.
Background m u tation rate ~ 1-6%
Radiation-induced ri sk of hereditary disorder estimated at
0.6 x 10 -2 /Sv/per person
Dose rate effect data from the “Mega mo use” Experiments at Oak Ridge National Laboratory.
Fe ta l Effe c t s
Lethal effects
Malformations
Growth disturbances
Principal factors
Dose
Gestation age at ti me of irradiation
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Data from rats given 200 rads at various time post-fertilization.
Japanese atom ic bomb survi vors irradiated in utero.
Grow th retardation : height, weight an d head diameter
Mental retardation: observed in children irradiated at 8-15 weeks (only) of pregnancy.
Effects observed at d o ses as low as 0.06 Gy.
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Cat a ract s: any detect able ch ange in the norma lly transparent lens of the eye.
Determini s tic respo nse
Cells are p r oduced by m itosis in th e germination zone (GZ) of the epithelium.
Differentiate into lens fibers in the meridional rows (MR).
Cells in the central zone (C Z) do not normally divide.
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No blood suppl y.
No mechanism for rem oval of dead or damaged cells.
Abnorm a l fibers m i grate towards the post e rior pole, the beginning of a cat aract.
Single doses > 2 Gy will cause cataracts.
Fractionation and low dose rate incr ease the threshold to 4-5 Gy.
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Estimation of risk from radiation exposure
Excess risk: the excess cas es of a particular health effect ass o ciated wi th exposure t o radiation. Excess risk can be described in various ways:
Absolute Risk: the difference in the rate of occurrence of a particular health effect in an exposed populati on and an equivalent population with no radiation exposure. (uni t s : excess num ber of cases pe r person-year-sievert).
Rel a tive Risk: the ratio of the rates in exposed and unexposed populat ions (dim ensionless)
Excess Relative Risk (ERR): the ratio of the rate difference to the rate in an unexposed population (N.B., ER R = the relative risk m i nus 1)
Excess risks depend on:
radiation dose
age at exp o sure
time since exposure
current age
gender
Risk esti mates are us ually reported for a sp ecific dose (often 1 gray or 1 sievert).
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[Image removed due to copyright considerations]
Estimates based on a m odel that acc ounts for age at exposure and gender. The vertical dotted line represents no excess risk.
The solid vertical line represent s the excess relative risk for all cancers.
Cancer deaths between 1950 and 1990 am ong Life Span Study - Survivors with significan t exposure s ( > 0.00 5 Sv)
|
Dose Ran g e |
Nu mber of Cancer Deaths |
Estimated Excess Deaths |
Attributable Fraction (excess lifetime risk) |
|
0.005-0.2 Sv |
3 3 9 1 |
6 3 |
2 % (=100 x 63/3391) |
|
0.2 – 0.5 Sv |
6 4 6 |
7 6 |
1 2 % |
|
0.5 – 1 Sv |
3 4 2 |
7 9 |
2 3 % |
|
> 1 Sv |
3 0 8 |
1 2 1 |
3 9 % |
|
All |
4 6 8 7 |
3 3 9 |
7 % |
Excess Lifetim e Risk
Bas ed on observed cancer inci dence to d a te
Depends on dose, age at exposure, sex.
Lifeti me cancer risks for atomi c bo mb survivors who received an acute dose of 0.2 Sv
|
Age at exp o sure (years) |
Excess lifetime risk |
Background lifetim e risk |
Excess relative risk (ERR) |
|
M E N |
|||
|
1 0 |
0 . 0 3 |
0 . 2 6 |
1 2 % (= 100 x 0.03/0.26) |
|
3 0 |
0 . 0 2 |
0 . 2 8 |
7 % |
|
5 0 |
0 . 0 1 |
0 . 1 8 |
6 % |
|
W O M E N |
|||
|
1 0 |
0 . 0 5 |
0 . 1 9 |
2 6 % |
|
3 0 |
0 . 0 3 |
0 . 2 0 |
1 5 % |
|
5 0 |
0 . 0 1 |
0 . 1 5 |
7 % |
(Data from http://www.r erf.or.jp )
Nu mbers of cancer deaths by cancer type and strength of evidence for a radiation effect
|
SITE |
TOTAL DEATHS |
ESTIMATED EXCESS |
EVIDENCE FOR EFFECT |
|
Stom a c h |
2 5 2 9 |
6 5 |
s t r o n g |
|
L u n g |
9 3 9 |
6 7 |
s t r o n g |
|
L i v e r |
7 5 3 |
3 0 |
s t r o n g |
|
U t e r u s |
4 7 6 |
9 |
m o d e r a t e |
|
C o l o n |
3 4 7 |
2 3 |
s t r o n g |
|
Rectum |
2 9 8 |
7 |
w e a k |
|
P a n c r e a s |
2 9 7 |
3 |
w e a k |
|
E s o p h a g u s |
2 3 4 |
1 4 |
s t r o n g |
|
G a l l b l a d d e r |
2 2 8 |
1 2 |
m o d e r a t e |
|
F. Breast |
211 |
37 |
strong |
|
O v a r y |
1 2 0 |
1 0 |
s t r o n g |
|
B l a d d e r |
1 1 8 |
1 0 |
s t r o n g |
|
P r o s t a t e |
8 0 |
2 |
w e a k |
|
B o n e |
3 2 |
3 |
m o d e r a t e |
|
Other solid |
948 |
47 |
strong |
|
Lym p h o m a |
1 6 2 |
1 |
w e a k |
|
Myelom a |
5 1 |
6 |
s t r o n g |
Statistical significance may v a ry, but ex cess risks are seen for all types of cancer.
Supports t h e notion t h at radiation increas es the risk for ALL t ypes of cancer.
Radiation in Medicine: therapy and diagnosis
a) thyroid cancer: 1930s and 1940s use of x-rays to shrink enlarged thym us in children.
b) Ringworm of the scalp: 1940s and 1950s x rays used to cause tem porary hair loss (several Gy), treat h a ir follic les more effectively. Increases in thyroid cancer, leukem i a, brain tum o rs (10,000 patients in Isra el, 2215 in New York).
c) In Britain, ~14,000 patients with a c ongenital spinal cord probl e m known as ankylosing spondylitis were irradi ated to relieve pain. Increased incidence of leukem i a.
d) Fem a le tuberculosis patie nts undergoing repeated fluoroscopy procedures showed an increas e i n breast cancer.
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Radium dial painters
Practice continued up to 1925. Ingestion of 226 Ra (b one seeker ) caused an increased incidence of bone cancer.
At autopsy, bone was analyzed for radium content.
Note, that there appears to be a thre shol d below which no effects are seen.
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What are the risks from low-doses of radiation?
All human data are relatively high dose and delivered at high dose rates…..
…..and extrapolate d dow n to the lo w dose region at low dose rates.
This is a source of s i gnificant and continuing controversy.
Risk Estimation Models
linear no-threshold
threshold
linear-quadratic
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The choice of model, and the estimate d risk , has serious implications for radiation protection.
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Data from high dose rate e xposures is extrapolated to low doses and low dose rates.
Low dose rate exposure is significantly less dam a ging.
Is there a 4 th curve??
Hormesi s
a term coined to describe the behavior of an agent t h at is lethal at high doses but
beneficial at low doses.
(e.g., nick el, chrom i um , hormones, ultraviolet light)
The radiation effects paradigm :
Radiation exposure i s harm ful.
Radiation exposure i s harm ful at all doses.
There are no effects at low doses that can not be predicted from the effects at high-dose levels.
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