Heriditary effects of Radiation kmio

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Heriditary effects of Radiation kmio

Heriditary effects of Radiation kmio

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  • 1. Hereditary Effects of Radiation
    • Presented by:
    • DR. SANDESH RAO B
    • on 03/08/2011 KMIO Auditorium
    • 1yr MD(Radiation Oncology Student)
    • MODERATOR:
    • Dr. Lokesh Viswanath M.D
    • Professor & Head of Unit II, Dept of Radiation Oncology
      • Kidwai Memorial Institute of Oncology, Bangalore
  • 2. GENETICS
    • 1944 – Avery, MacCleod, Mc Carty
    • - DNA – Heriditary material
    • Watson & Crick – Double helix
    • 1956 – Tjio, Levan
    • - Ford, Hamerton
    • - 46 chromosomes
  • 3. CHROMOSOMES
    • Long thread like structures – DNA
    • Carry all the information that specifies a particular human with all his/her individual characteristics.
    • 22 pairs of autosomes + 1 pair of allosomes.
  • 4. DNA
    • Double helix
    • Sugar phosphate backbone
    • Organic bases – A T C G
  • 5.
    • Gene – Finite segment of DNA specified by an exact sequence of bases.
    • Locus – Position of a gene
    • Human genome – DNA of chromosomes + DNA of mitochondria.
    • 6 billion base pairs of DNA.
    • Total no of genes – 50,000 to 1,00,000/haploid set of chromosomes.
  • 6. MUTATION
    • Any change in chromosomes, their genes, and their DNA.
    • Include an array of changes in DNA, such as deletion, rearrangement, breakage in the sugar-phosphate backbone, and base alterations.
  • 7. Hereditary Effects of Radiation
    • Adverse health effects in descendants due to mutations induced in germ cells.
    • Radiation does not produce new unique mutations, but increases the incidence of the same mutations that occur spontaneously.
    • Stochastic effect
    • Information on the genetic effects of radiation comes almost entirely from animal experiments.
  • 8.  
  • 9. Mendelian Inheritance
    • Autosomal dominant
    • Autosomal recessive
    • X-linked
  • 10. Autosomal dominant
    • Expressed in the first generation after its occurrence.
    • Polydactyly, achondroplasia, Marfan’s syndrome and Huntington's chorea.
  • 11. Autosomal recessive
    • Require that the gene be present in duplicate to produce the trait
    • Mutant gene must be inherited from each parent
    • Sickle-cell anemia, cystic fibrosis, and Tay-Sachs disease.
  • 12. X-linked
    • Mutations in genes located on the X-chromosome.
    • Hemophilia, color blindness, and a severe form of muscular dystrophy
  • 13.
    • 67% are caused predominantly by point mutations (base-pair changes in the DNA)
    • 22% by both point mutations and DNA deletions within genes (i.e., they are intragenic)
    • 13% by intragenic deletions and large multilocus deletions.
  • 14. Chromosomal Changes
    • Abnormalities either in the structure of the chromosomes or in the number of chromosomes
    • Down's syndrome
    • 40% of the spontaneous abortions
    • 6% of stillbirths
    • Radiation is much more effective at breaking chromosomes than in causing errors in chromosome distribution.
  • 15.
    • Irradiation induces a dose dependent delay in the entry of cells into mitosis & when cells that were irradiated while in interphase begins to divide some of reveal chromosome aberrations.
      • Chromosome aberrations
      • Chromatid aberrations
  • 16.  
  • 17.  
  • 18.  
  • 19. Multifactorial
    • 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
  • 20.  
  • 21. RADIATION-INDUCED HEREDITARY EFFECTS IN FRUIT FLIES
    • 1927 – Müller - exposure to x-rays could cause readily observable mutations in the fruit fly, Drosophila melanogaster .
    • Included a change of eye color from red to white, the ebony mutant with its jet-black color, the “vestigial wing” mutant, and the recessive lethal mutation.
  • 22.
    • Hereditary changes were considered the principal hazard of exposure to ionizing radiation because
      • A low doubling dose (5-150 R) for mutations
      • Hereditary effects were cumulative
      • Little was known of the carcinogenic potential of low doses of radiation.
  • 23. RADIATION-INDUCED HEREDITARY EFFECTS IN MICE
    • Russell and Russell - Oak Ridge National Laboratory
    • To determine specific locus mutation rates in the mouse
    • Megamouse project - 7 million mice
    • An inbred mouse strain was chosen in which seven specific mutations occur, 6 involving change of coat color & 1 as stunted ear.
  • 24.  
  • 25.
    • Five major conclusions
    • The radiosensitivity of different mutations varies by a significant factor of about 35
    • Dose rate effect was evident.
      • Chronic dose exposure induces fewer mutations
      • Acute dose exposure induces more mutation
      • This is in contrast with Drosophila
    • The male is more radiosensitive than females.
    • The genetic effects of a given radiation dose can be reduced greatly if a time interval is allowed between exposure and conception.
    • The estimate of the doubling dose adopted by BEIR V and UNSCEAR 88 is 1 Gy.
  • 26.  
  • 27. RADIATION-INDUCED HEREDITARY EFFECTS IN HUMANS
    • Two basic pieces of data are needed:
      • Base-line spontaneous mutation rate in humans – 738,000 per million.
      • The doubling dose (1 Gy, or 100 rad).
  • 28. Two Correction Factors
    • Not all mutations lead to disease.
    • The mutation component (MC):
      • 0.3 for autosomal dominant.
      • 0.0 for autosomal recessive.
      • 0.01-0.02 for chronic multifactorial.
    • The 7 specific locus mouse mutations are not representative; they are genes not essential for viability. Only a small proportion of human genes, when mutated, would result in live births.
  • 29.  
  • 30. Hereditary Effects − ICRP
    • Total population 0.2%/Sv
    • Working population 0.1%/Sv
    • Based on:
      • Hereditary risks for first two generations.
      • Life expectancy 75 yrs; reproductive age 30 yrs.
      • Total population 30/75 of reproductive pop.
      • Working population 30–18/70 of reproductive pop.
  • 31. Hereditary Effects of Radiation - Human
    • Children of the survivors of Hiroshima and Nagasaki have been studied for untoward pregnancy outcomes, death of live-born children, sex chromosome abnormalities, electrophoretic variants of blood proteins.
    • Though no genetic indication is statistically significant, the average doubling dose is 156 rem (1.56 Sv).
  • 32. MUTATIONS IN THE CHILDREN OF THE A-BOMB SURVIVORS
  • 33. References
    • Radiobiology for the Radiologist – Hall, Eric J.; Giaccia, Amato J.
    • Basic clinical Radiobiology – Gordon Steel
    • Radiation Biology – Donald Pizzarello
    • Clinical Radiobiology – Duncan, Nias
    • Clinical genetics – Laird G. Jackson, R. Neil Schimke.
  • 34.
    • THANK YOU