Keynote Lecture: Effects Effects on Tissues and …irpa12.org.ar/KL/I.2.2/Muller_pp.pdf · Keynote...
Transcript of Keynote Lecture: Effects Effects on Tissues and …irpa12.org.ar/KL/I.2.2/Muller_pp.pdf · Keynote...
Keynote LectureKeynote Lecture::
EffectsEffects on on Tissues Tissues and Organsand Organs ((including hereditary including hereditary and and prenatal effectsprenatal effects))
WolfgangWolfgang--U. MU. MüüllerllerInstitute ofInstitute of Medical Medical Radiation BiologyRadiation Biology
University Hospital EssenUniversity Hospital EssenGermanyGermany
StochasticStochastic
and and deterministic effectsdeterministic effects
dose-effect-relations
stochastic effect
deterministic effectseverityfrequency
(requires many damaged(=killed) cells)
(requires just one damaged(=modified) cell)
radiation dose
radi
atio
n ef
fect
Problem: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 experimentsAnimal experiments
Rodents are useful model systems for cataract research.In rats, 100 mGy are cataractogenic.Experiments with 25 and 50 mGy are in progress.
Cardiovascular EffectsCardiovascular 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 A possible mechanism for radiation possible mechanism for radiation induced cardiovascular problemsinduced 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.
A warning: Never look at one A warning: Never look at one mechanism only!mechanism only!
Adaptive
response
Bystander
effectGenetic
predisposition
Genomic
instabilityImmune defence
RepairNumber of mutations required
Apoptosis
Repair
systems inactive?
Some examples of important mechanisms:
Effects attributableEffects attributable toto prenatal prenatal exposureexposure::
TeratogenesisTeratogenesis and and mentalmental retardationretardation
Problem: Problem: ThresholdThreshold
dosedose?!?!
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).
OrganogenesisOrganogenesis ((malformationsmalformations):):100100--200 mGy200 mGy
Threshold dosesThreshold doses
(ICRP 90)(ICRP 90)
Fetogenesis (mental retardation):8.-15. week300 mSv300 mSv (= lower 95% confidence limit of
the point estimate of 600 mSv)
16.-25. week300 mSv300 mSv (= lower 95% confidence limit of
the point estimate of 900 mSv)
Threshold dosesThreshold doses
(ICRP 90)(ICRP 90)
IQIQ--ReductionReduction
Not definitely clear whether a threshold dose exists or not.IQ-reduction (without cases of severe mental retardation):
8.-15. Woche: 21 IQ-points/Gy16.-25. Woche: 13 IQ-points/Gy
Problem: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 Tissue weighting factor for gonads in the course of timein the course of time
ICRP 26 (1977): 0.25ICRP 60 (1991): 0.20ICRP 103 (2008): 0.08