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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