P1

Deterministic Effects

Severity increases with radiation dose (e.g., acute radiation syndrome, local tissue damage).

Stochastic Effects

Incidence increases with radiation dose (e.g., leukemia, cancer, genetic damage).

Radiation interactions occur at the atomic level, potentially leading to molecular changes.

Human Radiation Response

Atomic Composition of the Human Body

60.0% Hydrogen, 25.7% Oxygen, 10.7% Carbon, 2.4% Nitrogen.

 Molecular Composition of the Human Body

 80% Water, 15% Protein, 2% Lipids, 1% Carbohydrates, 1% Nucleic Acid.

Nucleus

Contains DNA (genetic material).

Cytoplasm

Bulk of the cell; contains organelles.

Mitochondria

The "engine" of the cell; produces energy.

Ribosomes

Site of protein synthesis.

Lysosomes

Contain enzymes for digesting cellular fragments.

Endoplasmic Reticulum

Channel for nucleus-cytoplasm communication.

DNA

Master molecule; double-helix structure with base pairs (Adenine-Thymine, Cytosine-Guanine).

RNA

Single helix; uracil replaces thymine. Includes mRNA and tRNA.

Protein Synthesis

Genetic message moves from DNA to mRNA, then to tRNA at the ribosome to form proteins via peptide bonds.

Mitosis

Process for somatic cells; includes Prophase, Metaphase, Anaphase, and Telophase.

Meiosis

Reduction division for genetic (germ) cells, resulting in 23 chromosomes.

High Sensitivity

Lymphocytes, spermatogonia, erythroblasts

Intermediate

Endothelial cells, osteoblasts, fibroblasts.

 Low Sensitivity

Muscle cells, nerve cells.

Stem cells

are more sensitive to radiation than mature cells.

Atomic Composition

0.2% Calcium, 0.1% Phosphorus, 0.1% Sulfur, 0.8% trace elements.

Metabolism

Sum of Anabolism (building) and Catabolism (breaking down).

Nucleolus

Found in the nucleus, contains RNA.

Cell Membrane

Provides structure and form.

Mitosis Detail

Metaphase is the stage where radiation-induced chromosome damage is most visible.

Cell Membrane

 Provides structure and form.

Mitosis Detail

Metaphase is the stage where radiation-induced chromosome damage is most visible.

Tissues

Muscle, nerve, connective, and epithelial.

Organ Systems

Nervous, Digestive, Endocrine, Reproductive, etc.

Law of Bergonie and Tribondeau

Stem cells are radiosensitive; mature cells are radioresistant.

Younger tissues and organs are more radiosensitive.

High metabolic activity and high proliferation rate increase radiosensitivity.

Specific Radiosensitivity High

Intestinal crypt cells.

Specific Radiosensitivity Intermediate

Osteoblasts, spermatids.

Specific Radiosensitivity Low

Chondrocytes.

ALARA

As Low As Reasonably Achievable.

Main-chain scission

Breakage of the backbone of the long-chain macromolecule. Reduces the size and viscosity of the solution.

Cross-linking

Production of small, spurlike side structures that attach to neighboring macromolecules or another segment of the same molecule. Increases viscosity.

Point lesions

Disruption of single chemical bonds. Not detectable, but can cause minor modifications that lead to cell malfunction.

In vitro

Irradiation outside of the cell or body.

In vivo

Irradiation within the living cell (macromolecules are more radiosensitive in their natural state).

DNA

is the most radiosensitive molecule.

Chromosome Aberrations

Terminal deletion , Dicentric formation , Ring formation

Radiolysis of Water

The human body is ~80% water; most radiation interaction occurs through water.

Hydrogen peroxide

 poisonous to the cell.

Dissociation

Water ionizes into an ion pair and free radicals

Free Radicals

Uncharged molecules containing a single unpaired electron in the outer shell. Highly reactive and unstable (lifetime < 1 ms).

Direct Effect

Ionizing event occurs directly on the target molecule (DNA).

Indirect Effect

Ionizing event occurs on a distant molecule (like water), which then transfers energy to the DNA via free radicals.

Principal effect on humans is indirect

due to high water content.

Key Molecule

DNA is the sensitive target molecule in the cell.

Cell Death

Occurs only if the target molecule is inactivated.

Hits

Radiation interaction with a target molecule is called a 'hit'. Hits occur through both direct and indirect effects.

Low-LET radiation (absence of oxygen)

Probability of a hit is low due to large distances between ionizing events.

Low-LET radiation (presence of oxygen)

Free radicals are formed, increasing the volume of effectiveness and the probability of a hit.

High-LET radiation

Ionizations are so close that the probability of a direct hit is high. Oxygen does not result in additional hits because the maximum number of hits is already produced.

Single-Target, Single-Hit Model:

Applies to simple biological systems like enzymes, viruses, and bacteria.

D37

The dose that results in 37% cell survival (63% lethality). It is a measure of radiosensitivity.

Multi-Target, Single-Hit Model

Applies to complex systems like human cells.

Implies a dose threshold.

Mean Lethal Dose

Constant related to radiosensitivity; dose that would result in one hit per target if no radiation were wasted.

Threshold Dose

Measure of the width of the shoulder of the curve; related to the capacity to recover from sublethal damage.

Extrapolation Number

Also called the target number.

Sublethal Damage

Accumulated damage before cell death. Cells can recover if doses are split (Split-dose irradiation).

Cell Cycle Sensitivity

Human cells are most radiosensitive in M phase.

Human cells are most radioresistant in late S phase.

RBE (Relative Biologic Effectiveness)

 Ratio of (x-radiation) to (test radiation) to produce the same effect.

OER (Oxygen Enhancement Ratio)

Ratio of (anoxic) to (oxygenated) to produce the same effect. OER is highest for low-LET radiation.

Acute Radiation Syndrome

Sequence of events following high-level radiation exposure leading to death within days or weeks.

Hematologic

2–10 Gy; survival 10–60 days. Characterized by reduction in WBCs, RBCs, and platelets.

Gastrointestinal (GI)

10–50 Gy; survival 4–10 days. Caused by damage to the lining of the intestines.

Central Nervous System (CNS):

>50 Gy; survival 0–3 days. Result of vasculitis and meningitis.

LD50/60

The whole-body dose that causes 50% of irradiated subjects to die within 60 days. For humans, this is approximately 3.5 Gy.

Robert Hooke

in 1665 named the cell as the biologic building block

Antonvan Leeuwenhoek

In 1673, accurately described

a living cell through his

microscopic observations

Schneider & Swann

In 1838, showed conclusively

that in all plants and animals,

cells are the basic functional

units.

Watson and Crick

Major Accomplishment:

1953, Description of the molecular

structure of DNA as the genetic

substance of the cell

HGP

Human Genome Project

Nucleic Acid

Rarest Molecule most critical and

radiosensitive target molecule

Dihydrogen Monoxide

H20

Catabolism

Breaking of Macromolecules to

Smaller units

Anabolism

Production of large molecules

from Small

Water

2 atoms of hydrogen

1 atom of oxygen

Homeostasis

Relative constancy of the human body’s internal environment

Perspiration and Respiration

Water is lost through?

Protein

Long-chain of macromolecules consisting of a linear sequence of Amino Acids

connected by peptide bonds

22 Amino Acids

Protein Synthesis utilizes how many amino acids?

2

how many amino acids to form protein?

Enzymes, Hormones, and Antibodies

proteins functions as?

1 Glycerol, 3 Fatty acid

Lipids is Composed of 2 smaller molecules

Antibodies

Primary defense mechanism of the body against

infection and disease.

Hormones

Molecules that exercise regulatory control of some

bodily functions e.g., growth and development

Hormones

Produced by the endocrine glands

Enzymes

Molecules necessary to allow continuation of biochemical reactions.

Lipids

Excess storage may lead to OBESITY

2:1 ratio of Hydrogen to Oxygen

In a Carbohydrate how many ratio

Lipids

Can be Catabolized into Glucose for Energy but is rather Difficult

Glucose

SUPER MEGA ULTIMATE Molecule that fuels the body.

RNA

Involved in growth and

development of the cell,

notably protein synthesis

DNA

Serves as command or primarily in Cytoplasm

control molecule for

cell function

DNA

If that cell is a GERM CELL,

all the hereditary information

of the whole individual

Interphase

Consists of g1 (pre-synthesis), S (DNA replication), and g2 (post-synthesis).

Mitosis (PMAT

Prophase (nucleus swells), Metaphase (chromosomes line up), Anaphase (chromosomes split), and Telophase (cytoplasm divides into two daughter

Meiosis

Results in four granddaughter cells, each with only 23 chromosomes.