DETERMINISTIC CHAPTER

EFFECTS 33
OF
RADIATION

SUBMITTED TO; MA’AM MARICEL P. GRANDE (DEAN)

SUBMITTED BY;ARVIN GABATINO

Early effect of radiation

 - to produce a radiation response in humans within a few days, to months, the dose must
be substantial such a response.

Deterministic radiation effects

-those that exhibit increasing severity with increasing radiation dose.

ACUTE RADIATION LETHALITY

-is the most devastating human response to radiation exposure.

ACUTE RADIATION-INDUCED HUMAN LETHALITY

-is of only academic interest in diagnostic radiology.

REMINDER!!!
Diagnostic x- ray beams always result in partial body exposure, which is less harmful
than whole body exposure.

Acute radiation syndrome

- events that follow high- level radiation exposure leading to death within days or weeks.
- Hermatologic death
- Gastro intestinal ( GI ) death.
- Central nervous system( CNS ) death.

Prodromal Period
- Acute clinical symptoms that occur with hours of exposure and continue for up to a say
or two.
- Approximately 1Gy delivered to the total body, signs and symptoms

Symptoms of early radiation sickness

- Nausea - reduction in the white blood cells of the peripheral blood
- Vomiting (leukopenia).
- Diarrhea

Latent period
 - After the prodromal period
- During which the subject is free of visible effects.
- Period of initial radiation sickness.
- A period of apparent well- being occurs.
- The time after radiation exposure during which there is no sign of radiation sickness.
- To indicate an early recovery from a moderate radiation dose.
- Can extend as long as 4 weeks.

Manifest illness
- Produce a given syndrome and the mean survival time.
- Principal measures of human radiation lethality.
- At very high radiation doses, disappears altogether.
- Characterized possible vomiting, mild diarrhea, malaise, lethargy and fever.

Hermatologic syndrome
- Radiation doses in the range of approximately 2 to 10 GY produce.
- Experiences mild symptoms of the prodromal syndrome.
- Characterized reduction in WBC and RBC and platelets.

Gastrointestinal syndrome
- Radiation doses of approximately 10 to 50 GY.
- Severe damage to the cells lining intestines.
- Measure able and even severe hematologic changes occur.

Central nervous system

- A series and symptoms occur that lead to death within a matter of hours to days.
- Causes of CNS elevate fluid content of the brain.
- Characterized by increasing cranial pressure, inflammatory changes of the blood
vessels of the brain ( vasculitis), and inflammation of the meninges ( meningitis ).
- Damage to all other organs of the body is equally severe.

LD 50\60
- Whole-body radiation dose that causes 50% of irradiated subjects to die within 60 days.
- Is measured quantitatively.
- Approximately 3.5 GY for humans.

Mean Survival Time

 - The average time between exposure and death decreases.
- Decreases from approximately 60 to 4 days.

Local Tissue Damage / Response

- Body is irradiated in contrast to whole body irradiation.
- Intrinsic radiosensitivity and the kinetics of cell proliferation and maturation.
Local Tissue can be affected immediately
-skin, gonads, and Bone marrow.

Effect on the skin

- Normal skin consist of three layers
• the epidermis – outer layer
•the dermis -intermediate layer of connective tissue
•subcutaneous layer of fat
•Connective tissue

- Skin additional accessory structures

•hair follicles
•sweat glands
•sensory receptors
Basal cells
- The outer skin layer, the epidermis, consist of several layer of cells.
- Lowest layer consists of basal cells
- Damage to basal cells results in the earliest manifestation of radiation injury to the skin.

Stem cells
-that mature as they migrate to the surface of epidermis.

The resultant skin damage

-erythema
- Sunburn like reddening of the skin.
- first observe biologic response to radiation exposure.
- Small doses of x-ray radiation do not causes of erythema.
-desquamation
- Ulceration and denudation of the skin.
- Moist desquamation is known as clinical tolerance.
Tinea capitis
- Persons with skin disease, such as ring worm.
- Which is common in children, was successfully treated by Grenz radiation.

Grenz rays resulted in permanent epilation

- Sometimes an unnecessary high dose on Grenz rays.

Effects on the Gonads

- Human gonads are critically importance target organs.
- They are particularly sensitive to radiation.
- These organs produce the germ cells that control fertility and heredity.

The cells of the testes/the ovaries

- Respond different to radiation in progression from the stem cell to the mature cell.

• ovaries and testes produce oogonia and spermatogonia which mature into ovum and
sperm, respectively.

Germ cell
- Produced by both ovaries and testes they develop from the stem cell phase to the
mature cell.

Gametogenesis
- Phase at different rates and at different times.

Oogonia
- The stem cells of the ovaries
- They multiply in number only before birth during fetal life.
 Primordial
- During late fetal life, grow to encapsulate the oogonia, which became oocytes.
- Contains oocytes remain in a suspended state of growth until puberty.

Ovum
- Only 400-500 ova are available for fertilization number of years menstruation times 13
per year.

The germ cell of the testes

- Continually being produced from stem cells progressive through a number of stages to
maturity and similar to the ovaries.

The male stem cell

-the male stem cell is the spermatogonia which matures into the spermatocyte in turn
multiplies and develop into a spermatid which finally differentiates into the functionally mature
germ cell the spermatozoa or sperm .

Irradiation of ovaries
- Life reduces the size (atrophy) through germ cell death. Irradiation of ovaries effect or
causes suppression and delay of menstruation.

The most radiosensitive cell during female germ cell development

- Is the oocyte in the mature follicle.

Spermatogonia stem cell

- Signify the most sensitive phase in the gametogenesis of the spermatozoa.

Male gametogenesis
- Is a self-renewing system.

Hematologic effects
-hematology lab
- once a week for a routine blood examination.
- this examination included total cell counts and a leukocyte different count.

Hemopoietic System
- Consist of bone marrow, circulating of blood and lymphoid tissue.
- Develop from a single type of stem cell. This stem called a pluripotential stem cell.
- Is another example of a cell renewal system.

Lymphoid tissue
- The lymph nodes, spleen and thymus.

Pluripotential stem cell.

- Develop into several different types of mature cells.

Spleen and thymus

- Manufacture one type of leukocytes

Lymphocytes
- Most circulating blood cells
- Manufacture of the bone marrow.

Active bone marrow

- Producing circulating cells is restricted to flat bones, such as the ribs, sternum, and skull
and the ends of long bones.
- Products of bone marrow stem cells
• lymphocytes – those involved in the immune response.
•granulocytes- scavenger type of cells used to fight bacteria.
•thrombocytes- also called platelets and involved in the clotting of blood to prevent
hemorrhage.
•Erythrocytes- red blood cells that are the transportation agents for oxygen.

Thrombocytes
- Lifetime approximately 5 days in the bine marrow.
Lymphocytes
- Produced over varying times and have varying lifetimes in the peripheral blood

Hemopoietic cell survival

- Radiation exposure is a decrease in the numbers of all types of blood cells in the
circulating peripheral blood.

Lethal injury to the stem cell

- Causes depletion of these mature circulating cells.

Lymphocytes
- These cell are reduced in number within minutes or hours after exposure, and they are
very slow to recover.

Lymphocytes and spermatogonia

- Are the most radiosensitive cells in the body.

Erythrocytes
- Less sensitive than the blood cells.

Cytogenetic effect
- Contributes enormously to human genetic analysis and radiation genetics.
- Culture of human cells to be prepared and treated the chromosomes of each cell can be
easily observed and studied.
- Study of the genetics of cells particularly cell chromosomes.

Radiation cytogenetic studied

- Shown that nearly every type of chromosome aberration can be radiation.

Chromosome abberrations
- Attempts measure in patient after diagnostic x- ray examination have been largerly
unsuccessful.
 - Some studies involving high dose fluoroscopy have shown radiation-induced.

Radiation – induced chromosomes aberrations follow a nonthreshold dose-response

relationship.

Chromosome aberration and latent illness or disease

- An even more difficult task is to identify the link between radiation-induced.

Normal Karyotype
- Can be cut out like a paper doll and paired with its sister into a chromosome map.
Each cell has 22 pairs of autosomes and the one pair on sex chromosomes -the female X-
chromosome and the male Y chromosomes.
Single Hit chromosome aberrations
- Can occur through direct and indirect effect.
- Hit this hit describe previously in radiation interaction with DNA.

A chromosome hit represent severe damage to the DNA.

Single-hit effects produced radiation duting G1 phase of the cell cycle breakage of a chrimatid is
called chrimatid deletion.

Chromosome with material missing from the ends of two sister chromatids and two acentric
fragments. These fragments called isochromatids.

A single chromosome can sustain more than one hit. Multihit aberrations are not uncommon.

Sickness
- The mechanism for the joining of chromatids depends on a condition. Is radiation-
induced and appears at the site of the severed chromosome.

Reciprocal translocations
- Are multihit chromosome aberration that required karyotypic analysis for detection.
Kinetics of Chromosome aberration
 - Very low doses of radiation, only single hit aberration occur.
- The general dose response relationship for production of single-hit and multihit
aberrations.

Some labaratories use cytogenetic analysis as a bilogic radiation dosimeter.

Human Genome
- 2000 the human Genome was mapped
- 35,000 genes distributed along the DNA the 46 chromosomes.

1. Define or otherwise identify the following

a. GI death

- Occurs because of the severe damage to the cells lining the intestines.

b. Latent period

- Is the time after exposure during which there is no sign of radiation sickness.

c. LD50/60

- Acute radiation lethality is measured quantitatively by the LD50/60 which is

approximately 3.2 GYT or 350 RAD for humans. Lethal dose of ionizing radiation for
humans is usually given as LD50/60.\

D. Erythema

- Sunburn like reddening of the skin.

d. Clinical tolerance

- Moist disquamotion is known as a clinical tolerance for radiation therapy.

e. Primordial follicle

- Primary oocyte center surrounded by flattened follicle cells which support oocytes.

f. Erythroecyte
- Total mass of circulating RBC’s and erythropoietic tissue of bone marrow. There is
usually a steady production that matches the destruction of RBC’s

g. Karyotype

- A test to identify and evaluate the size, shape, and number of chromosomes in a sample
of body cells.

h. Epilation

- Removes hairs from the follicles. Hair bulb swelling at the base of the follicle that
provides the hair with nourishment, it is thick, club shaped structure that forms the lower
part of the hair root.

i. Multihit eberration

- A chromosomal aberration resulting in a peculiar arrangement of chromosomal material

and representing severe chromosomal damage.

2. What is the minimum dose that results in reddening of the skin?

- 2Gy (200RAD)

3. Explain the prodromal syndrome.

- It is the period of acute clinical symptom that occur within hours of the exposure to
exposure to radiation and continue for a day or two

4. Clinical signs and symptoms of the manifest illness stage of acute radiation lethality
are classified into which three groups?

- Hemotalogic syndrome, gastrointestinal syndrome, central nervous system syndrome.

5. During which stage of the acute radiation syndrome is recovery stimulated?

- Prodromal period

6. What dose of radiation results in the GI syndrome?

- 10 to 50 Gyt

7. Why can death occur following the GI syndrome?

- Principally because of severe damage to the cell lining the intestines.

8. Identify the cause of death from CNS syndrome

- Elevated fluid content of the brain

9. Describe the stages of gametogenesis in a female. Identify the most radiosensitive

phases.

The most radiosensitive phases of gametogenesis in females are the stages of meiosis I
and meiosis II. During these stages, the chromosomes are most susceptible to radiation
damage, which can lead to chromosomal abnormalities and genetic mutations. The
primary oocytes are particularly sensitive to radiation during fetal development, which
can result in a reduction in the number of oocytes and potential infertility later in life. It is
important to minimize radiation exposure during these critical stages of gametogenesis
to prevent harmful effects on reproductive health.

10. What cells of the hemopoietic system arise from pluripotential stem cells?

- Lymphoid cytes, thrombocytes, erythrocytes, and granulocytes

11. Discuss the maturation of the basal cells in the epidermis.

Basal cell maturation.

User
Discuss the maturation of the basal cells in the epidermis.

ChatGPT
The basal cells are the innermost layer of the epidermis and play a vital role in the
maintenance of the skin barrier. They are responsible for producing new cells that
will differentiate and move up through the other layers of the epidermis to the skin’s
surface. The maturation of the basal cells is a complex process that involves multiple
stages of cell division and differentiation.

The first stage in the maturation of basal cells is cell division. Basal cells divide
actively to produce new cells, which will then differentiate into the other types of cells
that make up the epidermis. This process is regulated by various signaling pathways,
including the Notch and Wnt pathways.

After division, the newly produced cells undergo a process called stratification, which
involves moving up through the layers of the epidermis. As the cells move up, they
become increasingly specialized and acquire the characteristics of the different
layers of the skin.

The next stage is the differentiation of the basal cells into the specialized cells that
make up the upper layers of the epidermis. This process is driven by the activation of
specific genes and the production of different proteins, which give the cells their
 unique characteristics. For example, the basal cells differentiate into keratinocytes,
which are responsible for producing the tough, protective protein keratin.

Finally, the mature keratinocytes move up to the surface of the skin and are
eventually shed, as new cells are produced from the basal layer below.

The maturation of the basal cells is a tightly regulated process that is essential for
the maintenance of the skin barrier. Any disruption to this process, such as damage
to the skin or genetic mutations, can lead to a range of skin disorders, including
psoriasis, eczema, and skin cancer.

12. What two cells are the most radiosensitive cells in human body?

- Spermatogonia and lymphocytes.

13. Describe the changes in mean survival time associated with increasing dose.

In general, when examining the relationship between a certain dose and mean survival
time, there are different possibilities depending on the specific situation. For example, in
some cases, increasing the dose may lead to an increase in mean survival time,
whereas in other cases, it may lead to a decrease or no change in mean survival time.

It's also worth noting that any dose-response relationship needs to be analyzed and
interpreted within the context of the particular study design, population, and other factors
that may be relevant.

14. What is the approximately value of LD50/60 in humans?

- 3.5 Gyt (350 RAD)

15. What are the four principal blood cell lines, and what is the function of each?

- Erythrocytes (oxygen carrying cells)

- Lymphocytes (cells that are involved in immune response)

- Granulocytes (scavenger cells that fight bacteria)

- Thrombocytes (platelets that clot blood to prevent hemorrhage)

16. Diagram the mechanism for the production of a reciprocal translocation.

Two non-homologous chromosomes, labeled A and B, are present in a diploid cell.
 A double-strand break (DSB) occurs in both chromosomes, cutting the DNA at specific
sites.
The broken ends of chromosome A and B rejoin with each other instead of their
respective homologous chromosomes. This is called a reciprocal exchange or crossover
event.
The result is two derivative chromosomes, labeled AB and BA, each with a combination
of genetic material from both.

17. List the clinical signs and symptoms of hematologic syndrome.

- A reduction in cell count (especially lymphocytes), increased risk of infection, and loss of
electrolytes.

18. What mature cells form from the omnipotential stem cell?

- All somatic and genetic cells form from the omnipotential cell, the fertilized egg.

19. If the normal incidence of single hit type chromosome aberration is 0.15 per 100 cell
and the dose coefficient is 0.0094 how many such aberrations?

- =0.5/100

20. If the normal incidence of multihit chromosome aberrations is 0.082 and the dose
coefficient is 0.0047, how many dicentrics per 100 cells would be expected after a
whole body dose of 160 Gyt?

- =1.4/100