iii. physical mutagens heat causes molecules to move more

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



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.



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



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



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


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.




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



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

iii. physical mutagens heat causes molecules to move more

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