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semester 3  
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Lecture 7

Radiations Effect on Cells

Radiations Effects on Cells:

  1. Nothing Can Happen:
    • Gets absorbed and cells move on

  1. Cells die immediately (usually occurs at higher doses):
    • Dose Dependent – more photons interact, more ejected electrons, more hydroxy free radical being produced
    • Interphase Death – cannot be determined from normal cells death
    • Apoptosis – is the immediated, preprogrammed cell death (promt Lysis) is a normal function of cells
    • Over 1000 rads no cells will survive, this is the threshold

  1. Reproductive Death:
    • A group of cells in only considered viable if they can go through 5 Mitotic Cycles, if not they are no longer considered harmful

 

  1. Recovery – damage can be repaired (restitution – ELKIND repair)
    • Normal cells are more likely to repair (because of checkpoint gene in G2)
    • Only with theraputic doses

Theraputic Ratio:

Therapeutic ratio = NTTD / TLD

NTTD  - normal tissue tolerance dose

TLD – tumor lethal dose

  • The value you get for Theraputic Ration than 1 for teatment with Radiation to be considered
  • Can be manipulated with oxygen, or heat (hyperthermia)

 

Radiation Induced Chromosome Abberations

Hydroxyl Free Radical breaks the hydrogen bond in the Chromosome between  A:T (double bond) or G:C (triple bond) and causes damage to the chromosome

  • This leaves the chromosome wide open to
    • Recombine and fix itself (double breaks are harder to fix than single breaks)
    • Dissociate

CHROMOSOME ABBERATIONS (MUTATIONS) : is a changing in the base pairing of the chromosome. Radiation that is given early in Interphase, before the DNA synthetic period (S Phase).  The chromatid will have a break in a single strand of the chromatin, then during S Phase the chromatid will duplicate itself including the break which will result in 2 daughter cells with the same abberation

  • Can be good or bad
  • Takes places before DNA replication (S Phase 2n)
  • Has the possibility to pass on damage during Mitosis (both daughter cells will inherit the radiation injury)

 

CHROMATID ABBERATIONS:s a changing in the base pairing of the chromatid.  Radiation that is given during G2 after DNA replication (S  Phase).  The result will be one daughter cell showing the damage and the other one retaining its integrity.

  • Takes place after DNA has doubled (4n)
  • Creates 1 good cell and 1 damaged cell after Mitosis

These are two things that can happen if repair does not occur!!!

 

Three Types of Events Can Occur from the Interaction with Photons with Chomosomes:

  1. Single Break if 1 Arm:
    • chromosome most likely will repair (restitution)
    • inversion
  1. Single Break in 1 Arm of 2 Different Chromosomes:

The formation of Dicentric and Acentric fragments is a LETHAL EVENT:

      • There is a loss of genetic information
      • The chromosome cannot perform cytokinesis

Transolocation:

  • Genetic information switches
  • Is a mutation (can be good or bad)
  • NOT a LETHAL EVENT

  1. Double Break of 1 Arm

Deletion : the middle fragment of the two breaks is deleted from the arm

Inversion : the middle fragment of the two breaks is switched around causing the genetic information to be changed

  1. Double Break of 2 Arms of the same Chromosome

Inversion : the broken fragements can switch sides

Acentric Fragement and Ring Formation:

  • genetic information in lost to the acentric fragment
  • Ring Formation the 2 arms join together (when this happens 99.9% of the cells Die LETHAL EVENT)

  1. Single Break of 2 Arms of Different Chromosomes during Anaphase

Acentric Fragment : does not attach to the spindle resulting in a loss of genetic information

Anaphase Bridge : is formed between the two broken ends of 2 chromosomes on the spindle,  It will eventually break when the spindle migrate to the oppsite poles (LETHAL EVENT)

SUMMARY :

TYPE OF DAMAGE

SITE

ABBERATIONS

CONSEQUENCES TO CELL

Single Break

One arm of the chromosome

  • Restitution
  • Inversion
  • No damage
  • change in gene sequence; therfore possible functional alterations

Single Break

One arm of Two Chromosomes

  • Acentric and dicentric chromosomes
  • Translocation
  • Loss of genetic information; process repeated with eventual loss of major part of entire chromosome

Double break

One arm of one chromosome

  • Deletions
  • inversion
  • change in gene sequence; therfore possible functional alterations

Double break

Both arms of one chromosome

  • inversion
  • acentric fragments
  • ring formation
  • loss of genetic information; change in gene sequence, therefore possible functional alterations; possible severe cellular effects (eg death)
Single Break Both of of 2 chromosomes during Anaphase
  • acentric fragment
  • dicentric fragment
  • loss of genetic information; change in gene sequence, therefore possible functional alterations; possible severe cellular effects (eg death)