RADIATION BIOLOGY

RADIATION

• Radiation is a process in which a body emits energy that propagates through a medium, or through empty space, to be absorbed by other bodies.

TYPES OF RADIATION

• PARTICULATE RADIATION, which involves tiny fast-moving particles that have both energy and mass.

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•  Particulate radiation is primarily produced by disintegration of an unstable atom and includes Alpha and Beta particles

ELECTROMAGNETIC RADIATION

• Pure energy with no mass and is like vibrating or pulsating waves of electrical and magnetic energy.

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•  Produced by a vibrating electric charge and as such, they consist of both an electric and a magnetic component.

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• Electromagnetic radiation acts like a stream of small "packets" of energy called photons. 

• The massless photon particles each travel in a wave-like pattern. Each photon contains a certain amount (or bundle) of energy, and all electromagnetic radiation consists of these photons.
• The only difference between the various types of electromagnetic radiation is the amount of energy found in the photons.
• Electromagnetic radiation travels in a straight line at the speed of light

(3 x 10⁸ m/s).

��NATURE OF RADIATION��

1 IONIZING RADIATION

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•  Ultraviolet radiation
•  X-ray
•  Gamma radiation
•  Alpha radiation
•  Beta radiation
•  Neutron radiation

2 COSMIC RADIATION

3 NON-IONIZING RADIATION� . Non-ionizing electromagnetic radiation� . Ultraviolet light� . Visible light� . Infrared� . Microwave� . Radio waves� . Very low frequency (VLF)� . Extremely low frequency (ELF)� . Thermal radiation (heat)� . Black-body radiation

IONIZING RADIATION

• Ionization occurs when an electron is stripped (or "knocked out") from an electron shell of the atom, which leaves the atom with a net positive charge.

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• Originates from radioactive materials, X-ray tubes, particle accelerators, nuclear weapons, nuclear reactors, space (cosmic rays) and is naturally present in the environment, since most rock and soil has small concentrations of radioactive materials.  

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• Ultraviolet radiation

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> wavelengths from 10 nm to 125 nm

> ionizes air

> causes it to be strongly absorbed by air, ozone (O₃) in particular.

> biologically hazardous

> single photons of this energy cause electronic excitation of

biological molecules and damage them by unwanted reactions.

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• Example is the formation of pyrimidine dimers in DNA.

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• Unrepaired pyrimidine dimers may lead to MELANOMA.

• X-ray are electromagnetic waves with a wavelength less than about 10⁻⁹ m.
• smaller wavelength corresponds to a higher energy 

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• larger atoms are more likely to absorb an X-ray photon since they have greater energy differences between orbital electrons.
• soft tissue in the human body is composed of smaller atoms than the calcium atoms that make up bone.
• X-ray machines are specifically designed to take advantage of the absorption difference between bone and soft tissue.

• Gamma radiation- photons with a wavelength less than 3x10,⁻¹¹ meters 
• Gamma radiation emission is a nuclear process- to stabilize an unstable nucleus of excess energy
• Gamma rays can be stopped by a sufficiently thick or dense layer of material
• Alpha radiation-  helium-4 nuclei (two protons and two neutrons)

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• Alpha particles  interact with matter strongly due to their charges and combined mass
• At their usual velocities penetrate only a few centimeters of air, or a few millimeters of low density material 

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• Deflected by the Earth's magnetic field and then stopped by its atmosphere
• Do not penetrate the outer layers of dead skin cells and cause no damage to the live tissues below
• Eg: isotopes of radium, radon, and polonium.

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• Beta radiation- consists of an energetic electron
•  More penetrating than alpha radiation, but less than gamma

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• Occurs when a neutron decays into a proton in a nucleus, releasing the beta particle and an antineutrino

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• Neutron radiation- categorized according to their speed/energy.
• Consists of free neutrons.
• Emitted during either spontaneous or induced nuclear fission
• High-energy (high-speed) neutrons have the ability to directly ionize atoms.
•  Typically require hydrogen rich shielding, such as concrete or water, to block them within distances of less than a meter
• Cosmic radiation- high energy particles entering the Earth's atmosphere from outer space: the sun and deep space -  not yet well understood.

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NON-IONIZING RADIATION

• Kinetic energy of particles of non-ionizing radiation is too small to produce charged ions when passing through matter.

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• Non-ionizing electromagnetic radiation -  electromagnetic spectrum is the range of all possible electromagnetic radiation frequencies

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> Non-ionizing portion of electromagnetic radiation consists of - radio waves, microwaves, infrared, and (sometimes) visible light.

>Ionizing portion of electromagnetic radiation consists of – gamma rays, x-rays, uv rays.

• Ultraviolet light - lower part of the spectrum of ultraviolet, called soft UV, from 3 eV to about 10 eV - Non-ionizing.
• Visible light - very narrow range of electromagnetic radiation of a

wavelength that is visible to the human eye -  380–750 nm which

equates to a frequency range of 790 to 400 THz 

• Infrared - wavelength between 0.7 and 300 micrometer- 430 to 1 THz
• Microwave - one millimeter to as long as one meter- 300 GHz to 300 MHz.
• Radio waves, Very low frequency (VLF), Extremely low frequency (ELF), Thermal radiation (heat), Black-body radiation.

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RADIOBIOLOGY

• Study of the effects of ionizing radiation on living systems.

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STAGES IN BIOLOGICAL DAMAGE

• Damage can be broken down into 3 diff. frames:

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> PHYSICAL

> CHEMICAL

> BIOLOGICAL

PHYSICAL STAGE

• EFFECTS IN ATOMS & MOLECULES

EXCITATION IONIZATION

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MOLECULAR

DAMAGE

BREAKING OF MOLECULAR BOND

If enough molecules are damaged , then loss of function, impairment, or death of the cell may occur.

CHEMICAL STAGE

• RADIOLYSIS OF WATER

X- RAY ENERGY

H+ H2O2

HO- H+ HYDROGEN

WATER HO- H+ WATER

H2O O-

H2O* H+ H20

(HYDROPEROXYL) OH-

IONIZATION

RECOMBINATION

EXCITATION

BIOLOGIC STAGE

• Several things can happen to an irradiated cells:

> immediate cell death

> DNA damage

> No effect !

TYPES OF BIOLOGIC EFFECTS

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Changes in DNA

• Primary cause of radiation induced cell death, heritable mutations, cancer.
• Alterations include:

- breakage of one or more DNA strands

- cross-linking of DNA strands

- change or loss of base

- disruption of hydrogen bonds between DNA strands

• Germ line cells- involved- heritable defects.
• Somatic cell- involved- carcinogenesis.

DETERMINISTIC EFFECT

• Radiation injury to organisms results from killing of large number of cells.
• Eg: Mucositis resulting from RT to oral cavity.

Radiation induced cataract formation.

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STOCHASTIC EFFECT

• Radiation injury due to sub-lethal damage to individual cells that results in cancer formation or heritable mutation.
• Eg: Radiation- induced cancer

Heritable effect.

FACTORS INFLUENCING RADIATION EFFECTS

DETERMINISTIC EFFECT ON CELLS

• EFFECTS ON INTRA CELLULAR STRUCTURE

> NUCLEUS

> CHROMOSOME ABBERATIONS

• EFFECTS ON CELL REPLICATION

> DNA damage

> Bystander effect

> Apoptosis

• RADIOSENSITIVITY & CELL TYPE

> High mitotic rate

> Undergo many future mitoses

> most primitive in differentiation

CRITICAL ORGANS IN DENTAL RADIOGRAPHY

ACUTE OR SHORT TERM EFFECTS

• Effects appearing shortly after the exposure as a result of large dose
• Depends on sensitivity of parenchymal cells and proliferative rate

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• Dermatitis, epilation

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CHRONIC OR LONG TERM EFFECTS

• Effects appear after repeated exposure for a long period of time
• Depends on extent of damage to fine vasculature
• Carcinoma, Leukemia, Retardation of growth

RADIATION EFFECTS ON ORAL CAVITY

Oral mucous membrane

• Oral mucositis

5 stage model

1.Initiation of tissue injury: death of basal epithelial cells

2.Up-regulation of inflammation

3. Signaling and amplification

4. Ulceration and inflammation

5. Healing

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CLINICAL COURSE

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• Erythema of oral mucosa
• Ulceration
• White to yellowish psuedomembrane formation
• Secondary infections
• Mucosa heal within 2 to 4 weeks & become atrophic and thin
• Limited to tissues in the field of radiation

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MANAGEMENT

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• Pain control
• Nutritional support
• Oral decontamination
• Palliation of dry mouth
• Management of bleeding
• Anti-inflammatory agents
• Anti oxidants
• Low level laser therapy

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b. Taste buds

• are sensitive to radiation
• Loss of taste acuity at the 2^nd or 3^rd week of radiation
• Taste loss is reversible , recovery takes 60 to 120 days

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C. Salivary glands

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• Parenchymal component of SG is radiosensitive
• 1^st few weeks- a dose dependent marked & progressive loss of salivary secretion
• Zero at 60 Gy
• pH decreases
• Increased viscosity
• Composition - increased concentration of NaCl, Mg ions
• Xerostomia subsides after 6 to 12 month

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4. Teeth

children

• Irradiation before calcification –destroy the tooth bud
• After calcification has begun- inhibit cellular differentiation , causing malformations like retarded root devt, dwarfed teeth or failure to form one or more teeth
• Eruptive mechanism is radio resistant
• Adult teeth are resistant to direct effect of radiation exposure. Pulpal tissue demonstrate long term fibro atrophy

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• RADIATION CARIES

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• Rampant form

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Clinically 3 types of radiation caries

1.Most common-widespread superficial lesions

attacking buccal, occlusal, incisal &palatal surfaces.

2. Lesions primarily involving cementum & dentin in cervical areas.

3. Dark pigmentation of entire crown

• Teeth with gross caries or periodontal involvement are often extracted before irradiation

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5. Bone

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• Results from damage to fine vasculature of periosteum & cortical bone.

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• Destruction of osteoblasts & osteoclast

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• Normal marrow replaced with fatty marrow & fibrous CT.

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• Marrow tissue become hypovascular, hypoxic & hypocellular

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• Endosteum becomes atrophic

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3 H + trauma Osteoradionecrosis

Common in mandible

6. Muscles

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• Contracture & trismus in muscles of mastication – usually masseter &

pterygoid muscles are involved

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ACUTE RADIATION SYNDROME

• WHOLE BODY IRRADIATION

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Is a collection of signs & symptoms experienced by persons after acute whole body exposure to radiation

PRODROMAL PERIOD

• Within 1^st minutes to hours after exposure to

a dose of 1.5 Gy

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• GI disturbances like nausea , vomiting , diarrhoea , anorexia , weakness , fatigue

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• Dose related

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LATENT PERIOD

• Period of apparently well being

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• Extent is dose related

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• Extends from hours or days at supralethal exposure (>5Gy) to a few weeks at sublethal dose(<2Gy)

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HEMATOPOIETIC SYNDROME

• Dose 2 – 7 Gy cause injury to stem cells of bone marrow & spleen

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• Rapid decrease in no. of circulating granulocytes, platelets & finally erythrocytes

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• Clinically manifested as infection, hemorrhage & anemia

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• Death from haematopoetic syn. occurs 10 to 30 days after irradiation

GI SYNDROME

• When exposure of 7 – 15 Gy
• Injury to rapidly proliferating basal cells of intestinal villi – rapid loss of epithelial layer of intestinal mucosa – loss of plasma & electrolytes
• Loss of absorption , ulceration of mucosal lining with hemorrhaging into the intestine diarrhoea , dehydration, loss of weight etc.
• Endogenous intestinal bacteria Septicemia
• Death - within 2 weeks

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CVS & CNS SYNDROMES

• When exposure of more than 50 Gy
• Death results in 1 or 2 days
• Collapse of circulatory system with a fall in BP
• Necrosis of cardiac muscle

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• Also show intermittent stupor , incoordination disorientation & convulsions suggestive of extensive damage to CNS
• Death – within 2days

MANAGEMENT OF ARS

• Antibiotics
• Fluid & electrolyte replacement
• Whole blood transfusion to treat anemia
• Platelet administration
• Bone marrow grafts

EFFECTS ON EMBRYO & FETUS

• Exposure range of 2 – 3 Gy - first few days - undetectable death of embryo

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• Most sensitive period between 18 & 45 days of gestation -organogenesis occurs

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• Increased risk for childhood cancer after irradiation inutero

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• Dental radiography - 0.25micro Gy

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EXPECTED RISK OF CANCER

STOCHASTIC EFFECTS

• CARCINOGENESIS

- STIMULATING CELLS TO MULTIPLY

- LOSS OF FUNCTION

• LEUKEMIA < 20 yrs
• THYROID Ca – early childhood
• OESOPHAGEAL CANCER
• BRAIN & NERVOUS SYSTEM CANCER
• SALIVARY GLAND CANCER

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HERITABLE EFFECTS

• Radiation causes incresd frequency of spontaneous mutations rather than inducing new
• The frequency of mutations increases in direct proportion to the dose, even at very low doses, with no evidence of a threshold
• The majority of mutations are deleterious
• Dose rate is important
• Males are more radiosensitive
• The rate of mutation is reduced as the time between exposure and conception increases

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CONCLUSION

• Radiation is a double edged sword. It can produce both benefit & harm to a patient. So we should be aware of its hazards and handle it accordingly. The dental x –rays are not an exception.

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