Transcript Erstmaßnahmen nach Strahlenunfällen (1)

Keynote Lecture:
Effects on Tissues and Organs
(including hereditary and prenatal effects)
Wolfgang-U. Müller
Institute of Medical
Radiation Biology
University Hospital Essen
Germany
Stochastic and deterministic effects
dose-effect-relations
severity
frequency
deterministic effect
radiation effect
(requires many damaged
(=killed) cells)
stochastic effect
(requires just one damaged
(=modified) cell)
radiation dose
The cataract issue
Problem:
Until recently, it was thought that
radiation-induced cataracts emerge
only after exceeding a threshold dose of
about 1 to 2 Gy (acute exposure) or 5
to 7 Gy (chronic exposure).
It was overlooked that latency period
increases with decreasing dose.
Analyses show now that, if there is a
threshold dose at all, then it will be, at
least, tenfold lower than previously
thought.
Animal experiments
Rodents are useful model systems
for cataract research.
In rats, 100 mGy are cataractogenic.
Experiments with 25 and 50 mGy are
in progress.
The cardiovascular
issue
Cardiovascular Effects
Until recently, one assumed that
cardiovascular damage occurs after
high radiation doses only.
The most recent data from Hiroshima
and Nagasaki show that effects on
the cardiovascular system can be
observed, at least, down to 0.5 Gy.
A possible mechanism for radiation
induced cardiovascular problems
Radiation may damage the lining of small
vessels in the heart muscle leading to a low
oxygen level locally, and, after many years,
to slowly progressive fibrosis of the heart
muscle.
Bystander effect
method 1:
X
X
mediumtransfer
X
X
method 2:
X
X
X X
X
A warning: Never look at one
mechanism only!
Some examples of important mechanisms:
Adaptive response
Apoptosis
Bystander effect
Genetic predisposition
Genomic instability
Immune defence
Number of mutations required
Repair
Repair systems inactive?
Effects attributable to prenatal
exposure:
Teratogenesis and
mental retardation
Pregnancy risks
Gastroschisis
The threshold question
Pregnancy risks
Exencephaly
Problem: Threshold dose?!
For humans there are too few data to answer the
threshold dose question.
Many animal experiments were done with too few
animals to obtain a meaningful answer.
The bigger studies point to threshold doses in the
range of 50 to 250 mGy.
There are indications that sensitive sub-populations
exist in the total population (small, plateau-like effects
before the threshold dose is reached).
Threshold doses (ICRP 90)
Organogenesis (malformations):
100-200 mGy
Pregnancy risks
Severe mental retardation; SMR
[Source: ICRP 90 (2003) 105]
Threshold doses (ICRP 90)
Fetogenesis (mental retardation):
8.-15. week
300 mSv (= lower 95% confidence limit of
the point estimate of 600 mSv)
16.-25. week
300 mSv (= lower 95% confidence limit of
the point estimate of 900 mSv)
IQ-Reduction
Not definitely clear whether a threshold
dose exists or not.
IQ-reduction (without cases of severe
mental retardation):
8.-15. Woche: 21 IQ-points/Gy
16.-25. Woche: 13 IQ-points/Gy
Hereditary risk
Problem:
For humans, we only have some
data for the first and, partly, for the
second generation after radiation
exposure.
These data suggest a very low, if at
all, hereditary risk.
We do not have any human data for
the third and following generations.
Tissue weighting factor for gonads
in the course of time
ICRP 26 (1977): 0.25
ICRP 60 (1991): 0.20
ICRP 103 (2008): 0.08