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Transcript
IAEA Post Graduate Educational Course Radiation Protection and Safe Use of Radiation Sources Biological Effects of Ionizing Radiation Stochastic Hereditary Effects Genetic Effects of Radiation Lecture IAEA Post Graduate Educational Course Radiation Protection and Safe Use of Radiation Sources Introduction If the damage caused by radiation occurs in the germ cells - it may be transmitted and became manifested as hereditary disorders in the descendents of the exposed individual These are hereditary effects of radiation Add module code number and lesson title 2 Content Elementary genetics Natural mutations Induced mutations Sources of data for investigation of radiation induced mutations Doubling dose UNCEAR and ICRP approaches for genetic risk Add module code number and lesson title 3 Overview What are hereditary effects? Mutations must occur in the germ cells Change in the genetic materials must be transmitted to the descendents of exposed individual To be of genetic significance, gonadal irradiation must occur before or during the reproductive period Add module code number and lesson title 4 Hereditary effects: Definition Hereditary effect - a radiation-induced health effect that occurs in a descendant of the exposed person The less precise term ‘genetic effect’ is also used, but hereditary effect is preferred Hereditary effects are normally stochastic effects Add module code number and lesson title 5 Types of mutation Chromosome aberrations: alter the number of chromosomes, or alter structural arrangement of chromosomes often have very severe effects Gene mutations: affect a particular gene locus Add module code number and lesson title 6 Chromosome aberrations Numerical changes: Aneploid conditions (monosomies, trisomies) Structural changes: Translocations Deletions Add module code number and lesson title 7 Gene mutations Dominant Recessive Sex-linked Add module code number and lesson title 8 Natural frequencies in man Diseases Incidence per 1000 livebirths Chromosomal diseases Klinefelter's syndrome (XXY) (sterility, mental retardation) Turner's syndrome (XO) 1 0.1 Down's syndrome (trisomy 21) 1 Total incidence of chromosomal abnormalities 6 Add module code number and lesson title 9 Natural frequencies in man (Cont’d) Diseases Incidence per 1000 livebirths Dominant diseases Huntington's chorea 0.5 Polycystic disease of kidneys 0.8 Otosclerosis (deafness) 1 Hypercholesterolaemia 2 Overall frequency of harmful dominant and sex-linked conditions Add module code number and lesson title 10 10 Natural frequencies in man (Cont’d) Diseases Incidence per 1000 livebirths Recessive diseases Cystic fibrosis 0.5 Severe mental retardation 0.5 Severe congenital deafness 0.2 Overall frequency of harmful recessives 1 Add module code number and lesson title 11 Natural frequencies in man (Cont’d) Diseases Incidence per 1000 livebirths Sex-linked diseases Duchenne type muscular dystrophy 0.2 (in males) Haemophilia 0.1 (in males) Ichthyosis (skin) 0.1 (in males) Overall frequency in males Add module code number and lesson title 0.5 12 Induced mutations Ionizing radiation can induce mutations Induced mutations seem to be generally similar in nature to spontaneous ones No evidence for a threshold below which no mutations are induced Different types of germ-cell show differential radiosensitivity The yield of mutations depends on the dose rate, radiation quality, etc. Add module code number and lesson title 13 Doubling dose Doubling dose - the dose of radiation which, under a given set of circumstances, will give an overall mutation frequency which is double the spontaneous one The magnitude of this dose will depend on dose-rate, germ-cell type irradiated, etc Add module code number and lesson title 14 Source of data: induction of mutations in animals Observations: Chromosome aberrations: Dominant lethality Reciprocal translocations Deletions Add module code number and lesson title 15 Source of data: induction of mutations in animals (Cont’d) Observations: Gene mutations: Recessive mutations Dominant visible mutations Add module code number and lesson title 16 Source of data: induction of mutations in man Observations: Hiroshima and Nagasaki surveys: No significant increases in the frequencies of stillbirths, congenital defects, infant mortality, changes in birth-weight or sex-ratio or biochemical markers such as serum proteins Penitentiary inmates: Significant increase in the frequencies of translocation configurations in spermatocytes, from testicular biopsy material Add module code number and lesson title 17 Genetic risk Incidence, 10-2 Gy-1 (low LET)a Disease UNSCEAR, 1977 UNSCEAR, 1982 UNSCEAR, 1986/1988 Chromosomal anomalies 0.4 0.04 0.04 Dominant and X-linked 1.0 1.0 1.0 - - 0.15 0.45 0.45 - 1.85 1.49 1.19 Recessive Multifactorial Total a - assuming doubling dose of 1 Gy Add module code number and lesson title 18 Genetic risk (Cont’d) Incidence, 10-2 Gy-1 (low LET)a Disease ICRP, 1977 ICRP, 1991 Chromosomal anomalies 0.04 Dominant and X-linked 1.0 Recessive 0.15 Multifactorial 3.5b Total 2.0 2.4 a - assuming doubling dose of 1 Gy b - severity less than other genetic diseases, weighted by factor of 1/3 Add module code number and lesson title 19 Probability Coefficients for genetic risk, ICRP, 1991 Exposed population Hereditary defects, 10-2 Sv-1 Adult workers only 0.6 Whole population (all age groups) 1.0 Add module code number and lesson title 20 Summary This lecture presented materials about genetic effects of radiation The following topics were covered in the lecture: elementary genetics, natural mutation, induced mutations, sources of data for investigation of radiation induced mutations, doubling dose, UNCEAR and ICRP approaches for genetic risk Comments are welcomed Add module code number and lesson title 21 Where to Get More Information UNSCEAR, Sources and Effects of Ionizing Radiation, 2000 Report to the General Assembly with Scientific Annexes, United Nations, New York, 2000 International Commission on Radiological Protection. Publication N 60. Recommendations of the International Commission on Radiological Protection. - Oxford: Pergamon Press, 1991 IAEA Regional Basic Professional Training Course on Radiation Protection. SeptemberOctober, 1997. Germany, Training materials IAEA Training Course at IPSN. Medical Emergencies in Case of Radiological Accidents. November 1998. Training materials Add module code number and lesson title 22