ahmed group lecture 27 hereditary effects of radiation lecture 27

Ahmed GroupAhmed GroupLecture 27Lecture 27

Hereditary Effects of Radiation

Lecture 27Lecture 27


Single gene mutationSingle gene mutationChromosome aberrationsChromosome aberrationsRelative vs. absolute mutation riskRelative vs. absolute mutation riskDoubling doseDoubling doseHeritable effects in humansHeritable effects in humansRisk estimates for hereditable effectsRisk estimates for hereditable effects


Genetic diseases are attributed to mutations occurring in germ cells and are transmitted to progeny (hereditary diseases).Spontaneous mutation rates are increased by radiation exposure

Three principal categories of genetic diseases:

MendelianChromosomalMultifactorial


Mendelian Inheritance

Autosomal dominantAutosomal recessiveX-linked

Mendelian Diseases


Chromosomes

Homologous

Heterologous

Homozygous

Heterozygous


Process of DivisionSomatic Cells

Germinal Cells

Mitosis

Meiosis


Cell Division and Chromosome Number in

Sex Cells


Spermatogenesis

Spermatogonia

Primary spermatocytes

Secondary spermatocytes

Spermatids

Spermatozoa

Germ cell production in the male mammals


Oogenesis

Oogonia

Primary oocyte

Secondary oocyte

Ootids

Oocyte

Germ cell production in the female mammals


Chromosome Number


Chromosomal aberrationsGross abnormalities either in structure or number of chromosomes such as Robertsonian translocation, monosomy, trisomy and deletion.

Multifactorial diseasesDiseases known to have genetic component but also environmental factors:-Known to have a genetic component-Transmission pattern not simple Mendelian-Congenital abnormalities: cleft lip with or without cleft palate; neural tube defects-Adult onset: diabetes, essential hypertension, coronary heart disease-Interaction with environmental factors


Radiation induced hereditary effects

Children of Japanese survivors of atomic bomb attacks on Hiroshima and Nagasaki.

Relative versus direct mutation risk“If nature can do it, radiation can do it”.

In a set of genes:Av of spontaneous mutation rate

Relative mutation risk = Av of radiation-induced mutation rate


Megamouse Project

7 million mice were used

Five major conclusions1. The radiosensitivity of different mutations varies by a significant factor of about 35

1. Dose rate effect was evident.Chronic dose exposure induces fewer mutationsAcute dose exposure induces more mutationThis is in contrast with Drosophila


Five major conclusions continued

3. The male is more radiosensitive than females.

4. The genetic effects of a given radiation dose can be reduced greatly if a time interval is allowed between exposure and conception.

5. The estimate of the doubling dose adopted by BEIR V and UNSCEAR 88 is 1 Gy.

Megamouse Project


Doubling DoseThe doubling dose is the dose required to double the

spontaneous mutation rate.

• A low doubling dose (5-150 R) for mutations was estimated from fruit fly experiments.

• Hereditary effects are cumulative.

• Excess incidence of leukemia was evident but much larger number of solid tumors did not appear until many years later in Japanese survivors of the A-bomb attack.


Radiation and Sex Cells

• Resistant– Post-spermatogonial cells

• Sensitive– Stem cells

• Temporary sterility– 15 rad (0.15 Gy)– 40 rad/year (0.4 Gy/yr)

• Permanent sterility– 350-600 rad (3.5 to 6 Gy)– 200 rad/yr (2 Gy/yr)No significant hormonal imbalance

• Resistant– Post-oogonial cells

• Sensitive– follicles

• Permanent sterility– 250-600 rad (2.5 to 6 Gy)– 20 rad/yr (0.2 Gy/yr)

Pronounced hormonal imbalance

Males Females


Hereditary effects of radiation in humans

ahmed group lecture 27 hereditary effects of radiation lecture 27

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