iii. physical mutagens heat causes molecules to move more
TRANSCRIPT
The Genetics of Mutagens
The Genetics of Mutagens 1
III. Physical Mutagens
Dr. M. M. Daddona
A. Heat
Heat causes molecules to move more rapidly. DNAbreaks.
What types of mutations can be caused? Deletions, Translocations, Inversions
What kinds of mutagens will increase in activity? Tautomerisms, fragile sites, faulty enzyme activity
B. Radiation
There are two types of radiation: Particulate radiation Electromagnetic radiation.
1. Particulate Radiation
a. Alpha particles α 2p+ 2no
Positive particles shot out of an unstable nuclear area Causes? Attracts - parts of DNA, repels the + parts of DNA, DNA
breaks Types of Mutations
b. Beta particles β Electron-like particle β− Negative particles shot out of an unstable nuclear area Causes? Attracts + parts of DNA, repels the - parts of DNA, DNA breaks Types of Mutations
Deletions, Translocations, Inversions
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2. Electromagnetic Radiation Pure Energy. Travels in waves.
Longshort
The shorter the wavelength, the more energyyou are exposed to per second.
Electromagnetic Radiation
Ultraviolet Radiation Short electromagnetic wavelength Ionizing radiation H2O ----> H+ + [OH]-
DNA ----> pyrimidine dimers, hydrated cytosine,broken side chains.
What type of mutations?Deletions, Translocations, Inversions, Frameshifts
X-Rays
Shorter electromagnetic wavelength Released from the outer energy shells of an atom. Usually passes right through a cell without hitting
an e-. If an e- is hit DNA will vibrate violently, shoot
out and DNA breaks.
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X-Rays
When e- jump from higher energy shells intolower energy shells they release EM waves.
The energy is released from the electronshells of an atom.
We call these short λ , high energy waves =X-rays.
Stopped by lead.
X-rays
Gamma Radiation γ
Extremely short electromagnetic wave. Released from the nuclear area of an unstable
atom. Like X-rays, gamma rays can only be stopped
by lead.
Biological Effects ofRadiation Exposure
You are predominantly composed of WATER. Ionization of water causes the formation of ions
and free radicals.
H2O ------------> H+ + [OH]-
hydrogen ion hydroxyl radical
Causes?
Breakage Fusion Bridge
During Interphase chromatinmay break due to radiationexposure.
The piece with the centromereis called the Centric Fragment.
The piece without thecentromere is called theAcentric Fragment.
Centric Fragment
AcentricFragment
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Breakage Fusion Bridge During the S phase the
DNA is replicated. The broken ends will
stick together.
As the spindle fibersattached to thecentromere attempt toseparate the chromatidsduring Anaphase thefused ends cause theprocess to stall.
Centric Fragment
AcentricFragment
Breakage Fusion Bridge One of two possible
events will occur: The cell will not be
able to completemitosis and stopnuclear division.
A Giant Cell withexcess DNA willresult.
What happens to ahuman cell withexcess DNA?
Breakage Fusion Bridge
Or the Breakage-FusionBridge will tear.
Cytokinesis will occurand two cells will beformed.
One cell will have theacentric DNA out in thecytosol.
What will happen toeach cell?
What is the most commonresult of radiation
exposure?
Cell Death!
Which cells will die at thefastest rate?
Actively Dividing Cells
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Dividing CellsConstantly Dividing Cells1. Epithelial or Endothelial
Skin, hair, alimentary lining (mouth->anus),
Vascular lining, kidney tubules,Respiratory Tract, etc
2. Hemopoietic Stem CellsErythrocytes, neutrophils,
lymphocytes, megakaryocytes,etc.
3. Spermatogonia
Rarely Dividing Cells1. Neurons
Brain, sensory, spinal cord2. Muscle3. Bone4. Connective
Adipose, ligaments,tendons
5. Oogonia, Primary Oocytes
Measuring Dosage Roentgen - the amount of energy emitted based on number
of generated ionizations. Only defined in air for X-rays andgamma rays.
RAD - radiation absorbed dosage measures the amount ofenergy absorbed. 100 ergs
rem - roentgen (radiation) equivalent in man, evaluates extentof tissue damage.
X- or gamma rays = 1, alpha = 20
Gray - 100 RADS - Gy
Sievert - 100 rem - Sv
Biological Effects of Radiation Exposure
Dose(rem) Diagnosis (symptoms) <10rem no noticeable effects
10-50 rem Most people will notnotice any reaction, Sensitive people willexperience mildradiation sickness
PrognosisIncrease cancer riskPremature aging,Genetic, teratogenic effects
Premature aging, geneticeffects, increased risks oftumors
Biological Effects of Radiation Exposure
Dose(rem) Diagnosis (symptoms) 50- 150rem
Radiation Sickness: anemia, leukemia, reduced immunity, hemorrhaging, nausea,
vomiting, diarrhea, bloody,malnutrition, hair loss, dehydration,
red spider rash, lesions, dizziness, vertigo, burns
Prognosis
Usually most surviveWith medical aid,Reduced life spanIncreased cancer rateFemales sterile, males 2-3
years non-use.Genetic damage to offspring.
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Biological Effects of Radiation Exposure
Dose Diagnosis (symptoms)200rem Increase symptoms -
nausea, vomiting on first day, Fetal death
>300 LD50 Lethal Dosage 50%
>600 massive symptoms of radiation sickness
>1000 rem “Frying of Brain”
PrognosisDecreased life span, develop
cancer, teratogenic effects
50% die, 50% survive3-5 weeks aftermalignant cancer
Death in 10 days
Immediate Death
Sources of Radiation Exposure Natural Sources
1. Ground 28mrem/yr2. Wood 10 mrem/yr3. Brick 20 mrem/yr4. Cosmic rays = at sea level
27mrem/yr, higher 500mrem/yr5. Body K-40 20mrem/yr6. Ra-226 200mrem/yr, α7. NBR = 100 mrem/yr natural
background radiation, soil,cosmic, water, milk, nuts, cereal
Hot Spots - radiation caughtin cooling lava1. 350mrem France2. 1500mrem Kerala3. 1000 mrem Brazil4. 400 mrem Egypt higher 47,
??, +215. 180 mrem Denver6. 300 mrem Tibet7. 800 mrem Mt Everest
Sources of Radiation Exposure
Artificial Sources1. Fallout 15mr/yr2. Medical X-ray = new 39 mrem/exp. Old 100 mr/ exp
CT 25 mrem/exp3. Dental X-ray = 45 mr/exp4. Microwaves = ovens, remotes
Microwaves-WHO .1mW/cm2 telecommunications .01 worst in US over .1-10
US oven surface 1 Russia .01
Microwaves
One Hour of Microwave exposure duringair flight
approximately equals the amount ofenergy in
One X-ray exposure
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Repairing the Damage DNA Ligase -
DNA Polymerase β
Endonuclease -
UV Repair Enzymes -
Broken (P-D) side chains
Damaged bases Within DNA
Damaged base pairs within DNA
Dimers, Hydrations, Breaks
Exposure Recommendations
Health Physics Society Position Statement 5 rem per year or 10 rem in lifetime in addition to
NBR Based on current concept that NO Dose of exposure,
no matter how small, is without risk of cancer andgenetic damage.
Points to Note
There is NO threshold dosage forBiological Effects of Radiation!
There is NO expiration date forphenotypical appearance of post-
radiation effects!
The Effects of Mutagen Exposureare Cumulative!
Always Remember:
Over your lifetime