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

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.

method 1: method 2: Bystander effect medium- transfer X X X X X X XX X

A warning: Never look at one mechanism only! Adaptive response Bystander effect Genetic predisposition Genomic instability Immune defence Repair Number of mutations required Apoptosis Repair systems inactive? Some examples of important mechanisms:

Effects attributable to prenatal exposure: Teratogenesis and mental retardation 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 ).

Organogenesis (malformations): mGy Threshold doses (ICRP 90)

Pregnancy risks

Severe mental retardation; SMR [Source: ICRP 90 (2003) 105]

Fetogenesis (mental retardation): week 300 mSv 300 mSv (= lower 95% confidence limit of the point estimate of 600 mSv) week 300 mSv 300 mSv (= lower 95% confidence limit of the point estimate of 900 mSv) Threshold doses (ICRP 90)

IQ-Reduction Not definitely clear whether a threshold dose exists or not. IQ-reduction (without cases of severe mental retardation): Woche: 21 IQ-points/Gy 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