keynote lecture: effects on tissues and organs (including hereditary and prenatal effects)...

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