keynote lecture: effects on tissues and organs (including hereditary and prenatal effects)...
TRANSCRIPT
Keynote Lecture:Keynote Lecture:
Effects on Tissues and OrgansEffects on Tissues and Organs(including hereditary and prenatal effects)(including hereditary and prenatal effects)
Wolfgang-U. MüllerWolfgang-U. MüllerInstitute of Medical Institute of Medical Radiation BiologyRadiation Biology
University Hospital EssenUniversity Hospital Essen
GermanyGermany
Stochastic and deterministic Stochastic and deterministic effectseffects
dose-effect-relations
stochastic effect
deterministic effectseverityfrequency
(requires many damaged(=killed) cells)
(requires just one damaged(=modified) cell)
radiation dose
rad
iati
on
eff
ect
The cataract issueThe cataract issue
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.
The cardiovascular The cardiovascular issueissue
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 possible mechanism for radiation A 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.
method 1:
method 2:
Bystander effectBystander effect
medium-transfer
X
XX
X
X
X X XX
A warning: Never look at one A warning: Never look at one mechanism only!mechanism only!
Adaptive response
Bystander effectGenetic predispositionGenomic instabilityImmune defence
RepairNumber of mutations required
Apoptosis
Repair systems inactive?
Some examples of important mechanisms:
Effects attributable to prenatal Effects attributable to prenatal exposure:exposure:
Teratogenesis and Teratogenesis and mental retardationmental retardation
Pregnancy risksPregnancy risks
GastroschisisGastroschisis
The threshold questionThe threshold question
Pregnancy risksPregnancy risks
ExencephalyExencephaly
Problem: Threshold Problem: Threshold dose?!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).
Organogenesis (malformations):Organogenesis (malformations):
100-200 mGy100-200 mGy
Threshold doses (ICRP 90)Threshold doses (ICRP 90)
Pregnancy risksPregnancy risks
Severe mental retardation; Severe mental retardation; SMRSMR
[Source: ICRP 90 (2003) 105]
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 doses (ICRP 90)Threshold doses (ICRP 90)
IQ-ReductionIQ-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 riskHereditary risk
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 Tissue weighting factor for gonads in the course of timegonads in the course of time
ICRP 26 (1977): 0.25ICRP 60 (1991): 0.20ICRP 103 (2008): 0.08