Dangers of Radiation in Diagnostic Imaging

Introduction

       DANGERS OF RADIATION IN DIAGNOSTIC IMAGING is very important in oir life , let’s talk first about Radiation.

Radiation is a fact of life. Light and heat from the sun are natural forms of radiation essential to our existence.There are also other forms, which we generate in everyday life, such as microwaves for cooking, radio waves for communication, radar for navigation, and X-rays for medical examinations.

Radioactive materials also emit radiation.These materials occur naturally throughout the environment, but we have also produced others artificially.

We can classify radiation according to the effects it produces on the matter. There are two categories, ionizing and non-ionising radiations.

Ionizing radiation includes cosmic rays, X-rays, and the radiation from radioactive materials.

Non-ionising radiation includes ultraviolet light, radiant heat, radio waves, and microwaves.

we can also classify radiation in terms of its origin as natural radiation or artificial radiation.(1)

The benefits from natural non-ionising radiation, mainly heat, and light from the sun, are enormous, but there are no clear benefits from exposure to natural ionizing radiation.

We make considerable use of both lionizing and non-ionising radiation, however, Artificial radiations have led to dramatic advances In medical diagnosis and treatment, and are used for a wide range of procedures In Industry, agriculture, and research.

Nevertheless, they can be harmful to human beings and people must be protected from unnecessary or excessive exposures.

The greatest concern about ionizing  radiation stems from the way In which it can cause malignant diseases in people exposed to it and inherited defects In later generations.(2)

The likelihood of such effects depends on the amount of radiation that a person receives: this is equally true whether the radiation is natural or artificial.

So in circumstances that we can control, we need to make a careful balance between the risks and the benefits of the procedures that expose people to radiation.

The effects of non-ionising radiation depend on the type and intensity of the radiation.

Non-ionising radiation can damage the skin and the eyes, If it penetrates body tissues, It can damage internal organs by heating them in the long term, exposure to ultraviolet radiation may cause skin cancer and cataracts. Again we need measures to protect people from such effects.

As the effects of Ionising and non-ionising radiations have become better understood during recent decades, a system of radiological protection has been developed to protect people from sources of radiation.

The subject of radiation safety receives much attention In our society partly because radiation is one cause, among many, of cancer. Moreover, our senses cannot detect most forms of radiation; this undoubtedly adds to our anxiety.

Another reason for general concern may be the lack of reliable and accessible information about radiation. (3)

The Human Cell

The cell is the base unit of the life that reflect all its features (7).

It’s formed from the organic structure which is formed from macro-molecules, formed by a molecule which consists of atoms. In humans, there are approximately 1014 cells [8].

Cells can be simply divided into two categories: prokaryotic cells and eukaryotic cells [9].

The Prokaryotic cells don’t have a nucleus or membranous organelle (e.g mitochondria) but have nuclear membrane and ribosomes, so the DNA is found in the cytoplasm scattered, where they do their viral function. on the other side, The Eukaryotic cells have a nucleus and membranous organelles and, so divide by mitosis. [9].

To understand the effects of radiation on human beings. We should first study the human cell and its components very well.

Typical cell composed of a single nucleus (containing DNA molecules) embedded in cytoplasm and enclosed a cell membrane that selectively regulates the interchange of materials between the cell and its environment.(7)

 

Spiral staircase shape structure of The DNA27

DNA Structure: DNA is made up of subunits called Nucleotides, Each Nucleotide is made up of a sugar, phosphate and a base. There are 4 different bases in a DNA molecule: the first is Adenine (a Purine), the second is Cytosine (a Pyrimidine), the third is Guanine (a Purine), the fourth and the last is Thymine (a Pyrimidine).

We should note that number of Purine bases equals a number of Pyrimidine bases, and a number of Adenine bases equals the number of Thymine bases, also a number of Guanine bases equals the number of Cytosine bases.

The basic structure of DNA molecule is helical, with the bases being stacked on top of each other.

Cell Cycle

During its life, a cell generally exhibits a long period or phase (interphase) during which no division occurs, and a division phase (mitosis). This is called the cell cycle (10)

Cell Cycle can be divided into phases: G1 (gap), S (synthesis), G2 (gap), and M (mitosis).

Cells not actively growing to occupy a fifth phase known as G0, in which they can be stimulated to enter active cycle by environmental stresses. Cells are least sensitive when in the S phase (Resistance in

S phase may be due to the presence of synthetic enzymes capable of prompt repair of DNA breaks), then the G1 phase, then G2 phase as well as all cells in G0 phase and most sensitive in the M phase of the cell cycle. This is described by the law of Bergonie and Tribondeau, formulated in 1906. [10.11]

 

Active eukaryote cell divide through cell cycle stages28

 

BASIC INTERACTIONS OF RADIATION WITH MATTER:

We can classify the interaction according to two forms, either by energy of radiation or by site of energy deposition and interaction.

 

First, interactions according to the energy of radiation:  when radiation interacts with target atoms, energy is deposited, resulting in Ionization or excitation.

 

Now we will talk about interactions according to the site of energy deposition & interaction:

absorption of energy from ionizing radiation produces damage to molecules by direct and indirect actions, that will result in :

Direct Effects:

Damage occurs as a result of Ionization of atoms on target molecules in the biologic system e.g. DNA, RNA, ribosomes…

IONIZATION occurs at all radiation qualities but is predominant with High LET radiation, e.g. Alpha particles and Neutrons.there is considerable evidence suggesting that DNA is the primary target for Cell Damage from Ionizing Radiation.

Indirect Effects:

involves the production of reactive free Radicals in the medium in which cell organelles are suspended, whose toxic damage on Target molecule results in a Biologic effect. It’s is Predominant with Low LET radiation, e.g. X and Gamma rays. These are effects mediated by free radicals.

A free radical is an electrically Neutral atom with an Unshared (uneven) electron in the orbital position. The radical is electrophilic and highly reactive. Since the Predominant molecule in biological systems is Water, it is usually the intermediary of the radical formation and propagation.

Radiolysis Of Water:

 

Fate Of Free Radicals is one of the following: first rejoining each other causing no effect, as :

H0+ OH0 (free radicals) à H-O-H (H2o) which is not harmful

Secondly, Joining with other free radicals, as follows: Formation of Toxic Hydrogen Peroxide

(H2O2)which is very toxic; i.e. OH0 + OH0 à H2O2 (peroxide dimer)

Lastly, It can be transferred to an Organic molecule in the cell and Damaging it.

The Presence of dissolved oxygen can modify the reaction by enabling the creation of other free

radical species with greater stability and lifetimes.

 

Lifetimes of simple free radicals (H0 or OH0) are very short, on order of 10-10 sec.While generally highly reactive à they do not exist long enough to migrate from site of  formation to cell nucleus

However, Oxygen-Derived Species such as Hydroperoxy free radical does not readily, recombine into neutral forms. These more stable forms have a lifetime long enough to migrate to the nucleus where serious damage can occur.

FATE (RESPONSE) OF IRRADIATED CELLS ·

Irradiation of a cell will usually result in one of the following possible outcomes (responses):

First Division delay (Mitotic delay) in which Cell is delayed from going through division.

Secondly, Inter-phase death which occurs with high dose and insensitive phases.

Third , Reproductive failure in which Cell becomes incapable to undergo repeated division.

A) Division delay (Mitotic delay):

The cell is delayed from going through division; Length of delay depends on Cell Type, Dose Of Radiation and Dose Rate.the Cause of this delay is not Fully Understood but may be due to decreased DNA synthesis, or Prevention of Protein Synthesis needed for division. Alteration of Chemicals needed in the division process is also can be a cause. Another cause is mitotic Index, In a population of cells, Ratio Of No of cells undergoing mitosis (cell division) to No of cells not undergoing mitosis.

– Pre-Irradiation:

Mitotic Index shows Straight Line (Horizontal) and is Constant, this is because as some cells Complete mitosis, other cells Enter Division (same number).

– Post-Irradiation:

Radiation disturbs  Constant Ratio between  Dividing (Mitotic) Cells and  Non-Dividing (Non-Mitotic) Cells, this disturbance takes one of two forms;  Mitotic Delay (Decreased mitotic index), and Mitotic Overshot (Increased mitotic index). The mitotic delay is dose-dependent, At Low Doses After Irradiation Mitotic Delay occurs, followed by Mitotic Overshooting, then Mitotic Index Return to Pre-Irradiation state.

At High Doses, After Irradiation Mitotic Delay occurs and Mitotic Index Decreased and Cannot Return to Pre-irradiation state; because Reproductive Failure Occurs.

B) Interphase death:

The cell dies before entering the mitotic division.This occurs in non-dividing cells as well as rapidly dividing cells with high doses of radiation. The cell breaks fragmented into Smaller Bodies, taken up by Neighboring Phagocytes.

C. Reproductive failure:

It is the Inability of the Cell to undergo Repeated Division after irradiation. The Mechanism is due DNA and chromosomal damage.This Occurs With High doses of radiation.

CLASSIFICATION OF RADIATION DAMAGE14.15

Radiation damage to mammalian cells is divided into three categories Lethal, Sub-Lethal and Potential Lethal Damage.

A) Lethal Damage

It’s irreversible and Irreparable and can lead To cell death.(14,15)

B) Sub-Lethal Damage (SLD):

It is damages caused by a Sub-lethal dose of ionizing radiation, which can usually be repaired in hours Unless the additional sublethal damage is added.

It occurs when radiation is divided into small equal doses given to cell at separate time intervals (fractionation).

The Sub-lethal damage repair is a term used to describe the increase in cell survival seen if a given radiation dose is split into 2 equal fractions separated by a time interval.

If Dose is Split into 2 fractions separated by a time Interval, this leads to more cells survive than for the same total dose given in a single fraction, because the shoulder of the curve must be repeated each time.

High LET radiation, e.g., neutrons, is associated with little repair of SLD. Since Presence of a shoulder on a Cell Survival Curve is dependent on Quality of radiation used à Amount Of SLD Repair is similarly dependent on Quality Of Radiation.

Applications:

Sublethal damage repair is Of Significant Importance in the radiotherapy fields, as we can spare normal tissues from the effect of the therapeutic irradiation by fractionating the dose.

Example: Cells and Tissues with broad shoulder survival curves e.g. jejunum: shows a large amount of Sublethal damage and Repair: While other tissues e.g. bone marrow stem cells have Narrow shoulder survival curves, so they are more sensitive to irradiation & less amount of Sublethal Damage and Repair. (14,15)

diagram32

C) Potentially Lethal damage:

Component of radiation damage that modified by Post-Irradiation Environmental Conditions. It manipulated by Repair when cells are allowed to remain in a nondividing state.  Varying environmental conditions after exposing cells to X-rays: can Influence Proportion of cells that Survive a given dose due to Repair of PLD.

Damage considered Potentially Lethal since under ordinary circumstances leads to cell death. However, if Survival is increased following manipulation of the Post-irradiation environment, PLD is considered to have been repaired. (15)

 

FACTORS AFFECTING RADIOSENSITIVITY (RESPONSE) OF CELLS:

the response of the cells to radiation is affected by multiple factors, physical or biological or chemical …. In the following we will discuss some of it in few words:

 A) Physical Factors

1) LET (Linear Energy Transfer):

It is Rate at which energy is lost while traveling through matter; it differs according to the type of radiation ( the average amount of energy lost per unit of matter length).Measurement of the number of ionization which radiation causes per unit distance as it traverses the living cell or tissue.

In General, ALPHA Particles, which are relatively slow moving, have

a much higher LET than beta particles or GAMMA rays.BIOLOGICAL EFFECTS of High LET Radiations is higher than those of Low LET Radiations with the same energy. WHY?? This is because High LET radiation can deposit most of its energy within Volume Of One Cell of the body, Chance Of Damage to the cell is therefore Larger.Shoulder Region (in cell survival curve) is more Prominent with Low LET radiations.and is reduced and Slope becomes steeper with High LET radiations.(29)

diagram32

 

2) RBE (Relative Biological Effectiveness):

it’s comparison of a dose of some test radiation to a dose of 250 kV x-rays that produce a same biologic response. It’s used in Comparing effects of different types of radiation. e.x. RBE of Alpha Particles has been determined to be 20 -> This means that 1 Gy of ALPHA is equivalent to 20 Gy of GAMMAS/X-RAYS

RBE depends on LET (i.e. radiation quality), and Dose of radiation, Dose rate, Biologic system or endpoint, and Oxygen enhancement ratio (OER).Diagnostic X-ray has RBE of 1. RBE and LET have a relation as follow: increase LET, lead to increase  RBE,  till maximum effect (cell death) occur, then decrease RBE. If LET increases (with Constant factors), RBE will increase slowly at first, then more rapidly as LET > 10 keV/μm, RBE then increases rapidly to a peak value of 100 keV/μm, after which RBE decreases rapidly. (16,17).

diagram32

 

3) Dose rate (Protraction):

It is RATE the by which the radiation is delivered.it occurs with low LET radiations (with large shoulder curves) Only .in case of low dose rate, it allows Repair to occur before accumulated damages to the cell occur.If dose is Split into 2 fractions separated by time interval à More Cells Survive than for Same Total Dose given in a single fraction because shoulder of curve must be repeated each time.(7)

B) Biological Factors

 1) Stage of Cell Cycle:

Position of Cell in Its Cycle has a role in its response to radiation (Radiosensitivity). Cells are least sensitive when in S phase and most sensitive in M phase of cell cycle.

2) Intracellular Repair.

3) The degree of Differentiation:

Most Sensitive cells are those that are Undifferentiated, and Well Nourished, and Divide Quickly and is Highly Metabolically Active.

Most Sensitive body cells are Erythroblasts, Epidermal stem cells, and GIT stem cells. The Least Sensitives are Nerve Cells and Muscle fibers.

According to Law of Bergonie and Tribondeau that was set at 1906 by Bergonie and Tribondeau when they realized that cells were most sensitive to radiation when they are Rapidly dividing, Undifferentiated and have a long mitotic future

C) Chemical Factors

1) Oxygen effect:

Well, oxygenated tissues are more sensitive to radiation than Hypoxic Or Anoxic tissues.Oxygen enhances Cell Killing Effect of radiation.

Oxygen Enhancement Ratio (OER): it’s Ratio between Hypoxic and Aerated doses à to obtain the same biological effect.

Mammalian cells reach full Radiosensitivity before their full capacity of oxygen.

Effects of Oxygen are  Enhancement of free radicals formation, Increasing of stability and toxicity of free radicals, and Enhancement of cell division (mitosis), making the cell more sensitive.

OER is LET dependant: as ↑LET  → ↓OER.Effect of oxygen is More Obvious with Low LET radiations e.g. X-ray, Less Obvious with High LET radiations e.g. neutrons. Oxygenation of tissues à leads to shifting of Survival Curve to Left,

Hypoxia → leads to shifting Curve to Right.This effect is used to increase the effect of radiation therapy in Oncology Treatments.In Solid Tumors, the Inner parts become Less Oxygenated Than Normal Tissue.And Up to Three Times, higher dose is needed to Achieve the Same Tumor Control probability as In Tissue With Normal Oxygenation.(18)

Oxygenation and SF(7)

2) Radio-Sensitizing Agents:

drugs that make tumor cells more sensitive to radiation therapy e.g. Nitroimidazoles. (7).

3) Radioprotective agents:

Scavenging free radicals & producing hypoxia e.g. Thiols, do it can even worse than radiation. (29)

THE CELL SURVIVAL CURVE        

Cell Survival Curve is a curve that describes Relationship between Radiation Dose and Fraction of cells that survive. (i.e. fraction of irradiated cells that maintain their reproductive Integrity).

When Radiation Dose increases ⇒ Surviving cell fracture decreases constantly.Conventionally, the Surviving fraction is depicted on a logarithmic scale and is Plotted on the y-axis against dose on the x-axis.

Low Mammalian Cells:

Survival Curve shows constant slope i.e. equal increases of the dose causing a corresponding an equal decrease in Surviving Cell Fraction.

Every radiation dose is efficient to kill a fraction of cells, so the Response Curve is Linear.

Most Mammalian Cells:

Survival Curve exhibits a broad initial shoulder followed by a Steep Straight Slope. In Shoulder Region: Equal increases of the dose do not cause a corresponding equal decrease in the surviving cell fraction e.g. in the below curve < 2 Gy are inefficient to produce cell kill, indicating that damage must be accumulated before cell death.Below 2Gy dose, the curve show shoulder region.After a 2Gy dose, the curve becomes straight. (19,29,21)

                                                                                     

  diagram32

 Factors affecting the survival curve:

Linear Energy Transfer (LET) :

the first important factor as when it increases, the survival curves become steeper and decrease shoulder(progressively smaller).

The Second Important factor is RBE.

The Third Factor is Oxygen effect:

As Oxygenation of tissues leads to Shifting of the survival curve to the Left, while Hypoxia leads to shifting the curve to the right.the fourth and last factor is the dose Rate (Protraction) as follows: if the dose is split into 2 fractions separated by a time interval, this leads to more cells survive than for same total dose given in a single fraction, Because Shoulder of the curve must be repeated each time. (29)

TARGET THEORY

When Ionizing Radiation interacts with one of the essential (key) molecules, this is called Target.

The nucleus is more sensitive to radiation damage than Cytoplasm, thus implying that the Target for radiation is a Nuclear Constituent.

Since DNA is a molecule that controls all cellular activities, therefore DNA is the most likely target for radiation action.

Target Theory explains shoulder region in cell survival curve, AS Each cell, have a certain number of targets all of which must be hit to kill the cell. if one target is not hit à Cell will survive and repair the damage.13

STOCHASTIC AND DETERMINISTIC (NON-STOCHASTIC) EFFECTS                             

harmful effects of radiation may be classified into two general categories: STOCHASTIC and DETERMINISTIC (non-stochastic).

Stochastic Effect:

It’s Effect in which Probability Of Occurrence increases with increasing dose. Its severity in affected individuals does not depend on Dose.No Threshold The dose for stochastic effects, As these effects Arise In Single Cells.

Assumed that there is always Some Small Probability of the event occurring even at very small doses.Its Dose-Response Curve is a linear Quadratic relationship with No Threshold, it’s also Called Probabilistic.Examples: Induction Of Cancer, Radiation Carcinogenesis and Genetic Effects.12

Deterministic (Non-Stochastic)System:

It’s Effect on which The Occurrence depend On Threshold Dose i.e Below this Threshold Dose, the effect does

not occur.its severity increase with increasing dose,(above a threshold dose) in affected individuals.Threshold Value is variable for different cell systems & from one person to another.

These are events caused by damage to populations of cells, hence the presence of a threshold dose.

Its Dose-Response Curve is a Sigmoid relationship with a threshold. Examples: Fibrosis, Cataract, Acute Radiation Syndrome, Blood Changes and Decrease in Sperm Count (sterility).12

                                                                                                                                               

 diagram32

 

 

                                                                     

diagram32

Effects of Radiation on Developing Fetus.

Principal Effects of radiation on a fetus are: first, fetal or neonatal death. second Malformations. Thirdly, Growth Retardation. Fourthly, Congenital Defects. Fifthly, Cancer Induction. (31)

Between Conception and Birth, the fetus passes through three basic stages of development: Pre-implantation (day 1 to 10).Organogenesis (day 11 to 42).Growth stage (day 43 to birth). Effects of radiation on fetus depend on two factors, The dose and the Stage Of Development at the time of exposure. (6)

Pre-implantation ٍStage:

It is a stage from Concept (fertilization) up to 10 days (time of implantation), it is characterized by very rapid cell division making the stage very sensitive to radiation. (6)Effects of radiation in this stage are the Lethal effect (prenatal death), and Congenital anomalies (few).

Organogenesis Stage: (6)

It is a stage from the 10th day to 40 days; characterized by Organs Formation and Differentiation. During this stage: Incidence of Congenital Anomalies is increased especially in organs formed during this stage.

CNS and Special sense organs, and Skeletal and Muscular systems. Effects of radiation in this stage are Anomalies and malformations (mainly): e.g. CNS anomalies as microcephaly, spina bifida, hydrocephalus…. Etc. If these anomalies are Severe Enough, they lead to Abortion. (6)

 

Growth Stage:

It is the stage of fetal life after 40 days.Effects of radiation include Carcinogenesis (mainly): e.g. leukemia, retinoblastoma.Effects on developing fetus depend mainly on the dose of radiation and age of fetus when irradiated (stage). (6)

 

ABORTION: 

as a choice to avoid the possibility of radiation-induced congenital abnormalities should be considered only when the fatal dose has exceeded 10 cGy.Effect of 2-5 Gy of radiation differ as follows:

From 2nd to 3rd week: Prenatal Death.

From 4th to 11th week: severe congenital anomalies especially CNS and MSK system.

From 11th to 16th week: Mental Retardation, Microcephaly. After 20th week: Functional Defect.(6)

Acute Radiation Syndrome “ARS” (Whole Body Radiation).

Acute illness caused by a dose greater than 1 Gy of penetrating radiation to most or all of the body in a short time, usually a matter of minutes. ·

Hence, This syndrome needs 3 conditions to occur, Short exposure time (minutes), Total body exposure. External penetrating Radiation.

This syndrome includes a number of characteristic signs and symptoms whose severity depends on the magnitude of dose and duration of exposure.

Stages of ARS: according to the progression of illness through 4 stages:

Prodrome (the Prodromal stage):

Prodromal Symptoms has the following characters, it Occurs shortly after irradiation, Dose of exposure determine severity, duration, & onset. It may Last (episodically) for minutes up to several days. Its common prodromal symptoms include nausea, vomiting, anorexia, fatigue, diarrhea, abdominal cramping, and dehydration.severe and early onset of prodromal symptoms indicates higher dosage of exposure and a poor prognosis.it’s Progression through the other phases depends on the dosage of exposure.

Clinical latency (Latent stage):

In this stage, the Patient looks and feels generally Healthy for a few hours or even up to a  few weeks.

Manifest illness:

In this stage, the symptoms depend on the specific ARS syndrome.It Last from hours up to several months.

It ends in  Recovery or death.

Classic ARS syndromes  :

3 classic sub-syndromes:

1) Bone marrow syndrome (Hematopoietic system failure), It typically occurs after exposures of 2-10 Gy, death happened due to infection or huge at 4.5–6 Gy without supportive care. (23)At these doses, Lymphocytes and Precursor cells in Bone Marrow are destroyed, so preventing the new production of leukocytes and platelets.

2) During Few weeks (Clinical Latency), Circulating cells Die off with no replacements.

3) Manifest clinical stage, development of Infections.Possible Hemorrhage. Anemia from red cell depression. Management includes prevention of Infections: Antibiotics for infection, Isolation may be needed. Anemia: Transfusions as needed, Bone Marrow Transplantation.

Gastrointestinal syndrome:

Occurs after exposures of doses of 6-15 Gy. (23) Death of Intestinal mucosal stem cells in the crypts. (22)Common symptoms (manifest stage) include Anorexia, Nausea, Vomiting, Prolonged Bloody Diarrhea, Abdominal Cramps, Dehydration, and Weight Loss.m management: mainstays of treatment are Fluid and Electrolyte Balance and Infection.Prevention, but Death often follows in 7-10 days. (23)

CNS syndrome,

Occurs after exposures of more than 20 Gy. (23) If doses more than 100, so Death occurs within hours. Prodromal stage last few minutes. Symptoms include: Nausea, Vomiting, Hypotension, Ataxia, and Convulsions, and Death follow in a few days.Although the Exact mechanism of death is not fully understood, Vascular Damage is thought to lead to significant Cerebral Edema, producing Neurologic and Cardiovascular collapse. (23)

Effect of Radiation On Mammalian (Reproductive) Systems                          

Male Reproductive System

The sensitive reproductive organ is TESTES. The tissue of Testes is highly Radio-Sensitive as cells are rapidly dividing and are undifferentiated.

Main effects on testis are Infertility.Primary Effect of irradiation to Testes is Depletion Of Spermatogonia (especially type B), this leads to decreased Mature Sperms Count.

Temporary Sterility occurs if acute Dose of 2 Gy to Gonads of Adult Male, induces a temporary sterility which lasts a few months. Permanent Sterility: Acute Dose of 5 Gy to Gonads of Adult Male, induce Permanent sterility.

Of course, this is only for a Local Exposure because a whole-body dose of this magnitude would be Lethal. Chromosomal aberrations and genetic mutations occur in Spermatozoa and immature spermatogonia.

The Altered Genetic Information can be transmitted to the Next Generations.Note that The Male still retains the ability to engage in sexual intercourse, i.e. no impotence, so after radiation exposure to testis Patient should avoid sexual activity for 4 months till all cells at the time of irradiation disappear. (29)

 

Female Reproductive System:

The sensitive reproductive organ is OVARY.The tissue of Ovary is highly Radio-Sensitive as: cells are rapidly dividing and are undifferentiated.

Radio-Sensitivity of Ovary is Age-Dependent. Main effects on Ovary are Infertility, Temporary Sterility occurs when acute Dose of 2 Gy to Gonads of Adult Female, which leads to induces a temporary sterility, then start  Two months after irradiation (initial period of Fertility due to the presence of mature follicles that can give an Ovum).

Permanent Sterility occurs when Acute Dose of 6 Gy to Gonads of Adult Female, this induces Permanent sterility. Of course, this is only for a Local Exposure because a whole-body dose of this magnitude would be Lethal.

Chromosomal aberrations and genetic mutations occur in Oozoa and immature follicles.

The Altered Genetic Information can be transmitted to the Next Generations. Note that  Doses Causing Sterility in Females are higher than in Males, IRRADIATION of female genital system affect 2ry Sexual Characters e.g. causing menopause (due to Hormonal Disturbances). (29)

 

EFFECTS OF RADIATION ON THE EYE.   

EYE LENS is peculiar in that, as there is no cell replacement system, therefore damaged cells that have become opaque are not replaced naturally.

Radiation damage to EYE LENS shows a definite threshold effect (Deterministic =non-stochastic); does not occur below the threshold, but above threshold, increases Severity of the effect with increasing dose. Threshold Dose, Cataracts are induced, when dose more than 250-650 cGy is delivered to EYE LENS.

Above Threshold, increases  Severity of Cataract increases with increasing dose.Latent period, Radiation-induced cataracts may take many months to years (8 years) to appear.

Latent Period is Dose-Dependent; increasing dose will decrease the period.Features include Radiation-induced cataracts have Unique Features that distinguish them from senile cataracts.

The Earliest Changes include Diffuse Opacities (dots) around the Suture in the Posterior region.

Severity Of Opacities will Increase Gradually.Progression of Posterior Changes and involvement of the anterior sub epithelial region.Continued cataract development lead to entire Cortex is involved, but Posterior Capsule can still be discerned.

A 4+ cataract stage is one with Complete Anterior Opacification preventing visualization of the remainder of the lens.

The Pluses after the Score indicate the reality that a particular score at some given examination time reflects a cataract stage that was reached during the interval between the Previous and Current examinations.

Threshold Of Cataract Formation, Radio-sensitivity of the lens increases with age .24

 

Radiation Effect on DNA.  4

The BASE DAMAGE is Loss or change in The base of DNA which leads to Mutation.

SINGLE STRAND STREAK is Break in the Backbone of One Chain of DNA (mostly Easy repair), As the other chain act as a Template upon which the other chain repaired. DOUBLE STRAND STREAK is a  Break in both chains of DNA which leads to cell Killing, it’s difficult to be repaired.

Cross-Linking Occur Either within DNA molecule Or from One molecule to Another, which is Important of that lesion in Cell Killing is Un-Clear, But maybe important if not probably repaired.(4)

 

Radiation Effect on Chromosome. 

Chromosomal Damage Is Evident during Metaphase, Anaphase as chromosome is shortened & thickened.Radiation-Induced Chromosomal Breaks: Can Occur in both “Somatic & Germ cell”, and transmitted during Miosis & Mitosis.(4)

I) General Chromosomal Effect:

When Chromosome is exposed to Radiation, Breaking Occurs 2 or more chromosomal Fragments each of them having a broken end, then the broken end joins with the other end.

This will Possibly Produce New Chromosome, The new Chromosome May or May not appear structurally different from chromosome prior to radiation.

If It Occur, It occurs Either Before DNA Synthesis, this leads to Chromosomal Aberration “ Both daughter cells are affected”. or After DNA Synthesis: (G2-S Stage), this leads to Chromatid Aberration because Only One chromatid of pair has been damaged ⇒ One daughter Cell Affected. (29)

2) Types of Break:  

The first type is Single Break which occurs in One chromosome or chromatid.second type is Single Break occurring in Separate chromosome or chromatid.third type is Two or More Breaks occurring in the same chromosome or chromatid.last type is Stickiness or Climbing of chromosome or chromatid.

This Results In Consequences To the cells of these Structural changes may be one of the following.

First Restitution as Broken ends region with no visible damage. Secondly,  Deletion as Loss of a Part of chromosome or Chromatide, at the next mitosis gives rise to aberration.

Thirdly Re-arrangement of broken ends with Visible damage can produce grossly distorted chromosome. ( E.X 1) ACenteric Chromosome. ring Chromosome, Di-Centric Chromosome, and Anaphase Bridge.Re-arrangement of broken ends without Visible damage, this leads to Trans-location of Genetic Material Re-arrangement, which leads to Mutation. (29)

3) Chromosomal Sticking:

this occurs in a cell already in the division at Time Of Radiation.which leads to alteration of chemical composition Of Protein Chromosome, this results in Inability of Separation of Chromosome at Meta and Anaphase, Then Obride Formation between two opposite Poles.All lead to Error of Transmission of Genetic Materials of Daughter Cells.Change to the sequences of Genetic information, this occurs by “Trans-location and Inversion”. Both Processes requires 2 breaks either in the same chromosomal or different chromosomes. (29)

 

Radiation Effect on SKin.

LAYERS OF SKIN

Epidermis Outer layer of skin has two types of cell, Mature: Non-Dividing Cells, at the surface. And Immature: Dividing Cell of the base (Basal Layer). Cells lost from surface replaced by cells from the base layer which is Dividing, SO Skin is SENSITIVE TO RADIATION Dermis.: A layer of C.T which contain hair follicles, sebaceous gland, sweat gland, Bl.Vessels, Nutrition of skin.Sub-Cutaneous layer of C.T & Fat .(29)

 

I) Acute Effects:

when exposure to dose of 4-10 Gy, 2-3 Wks  after Radiation, this leads to Erythema & Inflammation, Dry Desquamation, and Moist Wet Desquamation.25,26

2) Chronic Effects:

Atrophy & Thinning of the epidermis, and Fibrosis, and increase pigmentation, ulceration, necrosis.Note that Fractionated dose of 60 Gy in 60 wks with high energy unit Radiation Produce Minimal Skin Effect in Chronic Changes, this leads to  Atrophy of Irradiated area. Severe Necrosis Rare to occur at practice.

 

Hair Follicles

it is actively growing tissue which is Radio-Sensitive.Temporary Hair Loss Occur at a moderate dose of 7 Gy.Permanent Hair Loss Occur at High Dose more than  7 Gy.Hair Loss Occur on the 7th day of radiation.

 

Salivary Glands

when exposed to  40 Gy. As they are sensitive to radiation after 1st Wk of radiation. Saliva is reduced frequently after a transient phase of hyper-salinization. Total Dose of Bilateral Salivary gland 40 Gy, this will stop salivary production. Chronic Xerostomia has an impact on quality of life.

 

Radiation to Mucosa causes Erythema, Edema, Patchy mucositis. Mucositis start after 3 Gy.26

 

EFFECT OF RADIATION ON SKIN(4)

 

 

RADIATION PROTECTION:

AFTER their discovery, x-rays were applied to the healing arts. It was recognized within months, however, that radiation could cause harmful effects.

The first American fatality that resulted from radiation exposure was Thomas Edison’s assistant, Clarence Dally.

Since that event, a great deal of the effort has been devoted to developing equipment, techniques, and procedures to control radiation levels and reduce unnecessary radiation exposure to radiation workers and the public.

The cardinal principles for radiation protection are simplified rules designed to ensure safety in radiation areas for occupational workers. In 1931, the first dose-limiting recommendations were made.

Today, the National Council on Radiation Protection and Measurements (NCRP) continuously reviews the recommended dose limits.

Providing radiation protection for workers and the public is the practice of health physics. Health physicists design equipment, calculate and construct barriers, and develop administrative protocols to maintain radiation exposures as low as reasonably achievable (ALARA).(29)

Structure materials, air, coolant waters etc. are activated in neutron fields. The induced activity has to be considered in radiation protection design of nuclear reactors, fusion experimental reactors, and high energy accelerators. (30)

The term health physics was coined during the early days of the Manhattan Project, the secret wartime effort undertaken to develop the atomic bomb.

The group of physicists and physicians responsible for the radiation safety of persons involved in the production of atomic bombs were the first health physicists.

Thus, the health physicist is a radiation scientist who is concerned with the research, teaching, or operational aspects of radiation safety At the turn of the Millennium, the year 2000, the National Academy of Sciences identified the 20 greatest scientific and technical accomplishments of the 20th century.

Medical imaging was number 14 on this list.This is important to point out to our patients, many of whom remain wary of radiation. One never reads the word “radiation” in a newspaper or a magazine without the modifier “dangerous,” “deadly,” or “harmful.”

We practice ALARA because of the linear no-threshold radiation dose-response relationship (LNT) for stochastic effects—cancer, leukemia, and genetic effects.

Yet we should also recognize that we actually employ low levels of radiation in diagnostic imaging.Unquestionably, the application of this radiation has had a major impact on our health and increasing longevity.

If you had been born in the United States in 1900, your life expectancy was 47 years. During the first century of diagnostic x-ray imaging, life expectancy has soared.

Life expectancy is now 78 years (Figure BELOW).Nevertheless, because of LNT, we must continue to be aware of patient and occupational radiation dose and must take those steps necessary to implement ALARA.(29)

Life expectancy as a function of year of birth.(29)

Conclusion

We can summarize the previous article that Radiation is a double way weapon, it can be used in the diagnosis and treatment of different body diseases. but it must be used carefully as it has many side effects that may turn the simple diagnosis maneuver into fatal disease . to reach to good knowledge of the harmful effect of radiation on human body we discuss the basic unit of the body, the cell. and we discuss the radiation interaction, effect of radiation on different body systems.

 

 

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2 thoughts on “Dangers of Radiation in Diagnostic Imaging

  1. Larhonda Fraschilla February 20, 2018 at 5:01 am

    This content is amazing!

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