Module III.4.1-Stochastic hereditary effects

Download Report

Transcript Module III.4.1-Stochastic hereditary effects

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