Radiobiology and Radiobiology and Physics in Cancer Physics in Cancer

TreatmentTreatment

Dr. Vic MontemayorDr. Vic MontemayorDepartment of Physics & AstronomyDepartment of Physics & AstronomyMiddle Tennessee State UniversityMiddle Tennessee State University

An Introduction to An Introduction to PHYS 3600PHYS 3600

History: Discovery of X-rays

Wilhelm Röntgen: 1895

Timeline of Events:• 1896: first radiograph

• 1896: first medical application

• 1897: first therapeutic use

First Radiograph (1896)

Radioactivity

Timeline of Events:• 1898: discovered by Becquerel

• 1898: radium isolated by Pierre and Marie Curie

• 1901: first recorded intentional experiment in radiobiology performed by Pierre Curie

Radiobiology

Radiobiology: the study of the effects of ionizing radiation on living tissueIonizing radiation results in a localized absorption of a relatively large amount of energy in tissue.ave energy released in ionizing event in tissue

= 33 eV

typical chemical bond in tissue = 5 eV

(C=C bond energy = 4.9 eV)

Radiobiology

Types of Ionizing Radiation:

1. Electromagnetic Radiation

x-rays, gamma rays

Radiobiology

Types of Ionizing Radiation:

2. Particles

charged: electrons, protons, particles, heavy nuclei

uncharged: neutrons

Critical Target of Radiation Treatment

DNA!

The biological effects caused by radiation result primarily from damage to the DNA.

Two Categories of Ionizing Radiation

1. Directly Ionizing Radiation– has sufficient kinetic energy to change the atomic structure of the material through which it passes, thereby producing chemical and biological changes; charged particles are in this category

Two Categories of Ionizing Radiation

1. Directly Ionizing Radiation– has sufficient kinetic energy to change the atomic structure of the material through which it passes, thereby producing chemical and biological changes; charged particles are in this category

2. Indirectly Ionizing Radiation– does not produce chemical or biological damage directly, but rather gives up its energy in the release of energetic electrons that can then result in chemical and biological change; electromagnetic radiation is in this category

Direct Action of Photons

• incident photon releases energetic electron that then produces an effect in DNA

Indirect Action of Photons• incident photon

ionizes water molecule resulting in hydroxyl radical ( ) which diffuses to and interacts with DNA

About 2/3 of x-ray damage to DNA is caused by the hydroxyl radical!

OH

Production of Biological Effectsincident

photonresults in

ion radical (H2O+)

releases fast electron

chemical changes in DNA from broken bonds biological

effects resulting from damaged

DNA

production of hydroxyl radical

2 2

3

H O H OH O OH

1010 s

Time Scale for Biological Effects

cell killinghours to days (when damaged cell tries to

divide)

oncogenicovert cancer may not appear for 40 years or

more

mutation resulting in inheritable changes

may take up to many generations

Damage to DNA

• double strand breaks are thought to be the most important contribution to cell killing, mutation, or carcinogenesis

• single strand breaks are readily repaired

DNA bases :adenine thymine guanine cytosine

The Cell Cycle

Teachline, The Hebrew University of Jerusalem (Alexander Silberman Institute of Life Sciences)

Phases of the Cycle:•G1: growth and preparation of chromosomes for replication

• S: synthesis of DNA

• G2: preparation for mitosis

• M: the production of two separate cell nuclei (mitosis) and the subsequent pinching off of the cell membrane to produce two daughter cells (cytokinesis) (the M phase lasts about 1 h)

The Cell Cycle

Teachline, The Hebrew University of Jerusalem (Alexander Silberman Institute of Life Sciences)

Hamster Hamster Cells (h)Cells (h)

HeLa HeLa Cells (h)Cells (h)

MM 11 11

G1G1 11 1111

SS 66 88

G2G2 33 44

1111 2424

HeLa Cells: cervical cancer cells taken from Henrietta Lacks (died: 1951) forming an immortal cell line used in research

Measurement of Cell Survival

Cells are seeded in a dish and incubated for 7 days.A. 100 cells seeded; 70%

plating efficiency (70 colonies survive)

B. 2000 cells seeded and exposed to 8 Gy of x-rays (32 colonies survive)

Generic Cell Survival Curves

FYI: Mammalian vs. Microorganisms

A. mammalian cells

B. E. coli

C. E. coli B/r

D. yeast

E. phage staph E

F. B. megatherium

G. potato virus

H. Micrococcus radiodurans

Radiosensitivity with Cell-Cycle Phase

* time scales have been adjusted to that the S phase is comparable in both cell lines

General Characteristics:

• cells are most sensitive around M

• resistance is usually greatest in latter part of S

• for longer G1 phases, early resistance is followed by sensitive period

• G2 is about as sensitive as M

(This is studied using the mitotic harvest technique.)

Cancer Treatment Modalities using

Radiation− brachytherapy

uses radioactive “seeds”

− radiation therapy

using photon or charged particle beams

Cancer Treatment Modalities using

Radiation− brachytherapy

uses radioactive “seeds”

− radiation therapy

using photon or charged particle beams

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