RADSCI 4670 - exam 1

cell

- basic structural, functional, biological unit of all living organisms

- humans = eukaryotic

cell theory

1. all living things are made of cells

2. the cell is the most basic unit of life

3. all cells come from pre-existing cells

organic components

- contains a carbon (hydrocarbon = hydrogen + carbon)

- ex: proteins, carbs, lipids, nucleic acids

inorganic compounds

- do NOT contain carbon

- osmotic balance

- nerve conduction

- muscle contraction

- enzyme activation

- pH buffering

- radiation can cause ion imbalances from membrane damage & disrupts cell signaling

- ex: mineral salts (sodium & potassium), water

nucleic acid

- DNA & RNA

- radiation causes strand breaks

cell membrane

- monitors & controls the movement of everything going in / out of the cell

- composed of lipids & proteins --> nonrigid

- maintains structure

cytoplasm

- gel-like substance between the nucleus & cell membrane

- contains organelles

- site of all metabolic functions

nucelus

- serves as the info & administrative center of the cell

- stores DNA

- coordinates cell's activities

- nuclear membrane separates the contents of the nucleus from the cytoplasm

nucleolus

makes ribosomes

ribosomes

- made up of proteins (40%) and RNA (60%)

- site of protein synthesis

endoplasmic reticulum (ER)

- "highway of the cell", "network of tubes" --> internal delivery system

- proteins synthesized by ribosomes move through the ER to the golgi apparatus

- types = rough or smooth

rough ER

- has ribosomes

- protein synthesis

- intracellular transport

smooth ER

- does NOT have ribosomes

- lipid synthesis

- carbs metabolism

- detoxification of drugs & poisons

protein synthesis

- nucleus sends message to cytoplasm indicating which protein needs to be made

- message (in the form of code) is carried by mRNA to the ribosome

- ribosome reads message & translates it (using tRNA)

- ribosomes assemble amino acids in their proper sequence to form the specific protein

- protein is released from the ribosome

- DNA --> RNA --> protein

golgi apparatus

- packaging area for products manufactured by the cell for export

- prepares proteins for export

- carbs synthesis

- binds organic compounds to proteins

mitochondria

- powerhouse

- produces energy for cellular functions by breaking down nutrients (process called oxidation)

lysosome

- digestion

- breaks down proteins, DNA, carbs

cell division

- mitosis = somatic cells

- meiosis = germ cells

somatic cells

- all other cells (besides germ)

- divide by mitosis

- contains diploid # of 2n # (46 chromosomes)

germ cells

- sexually reproducing cells

- divide by meiosis

- contains n# or haploid # (23 chromosomes)

mitosis

- 1 parent cell divides to form 2 daughter cells

- prophase --> metaphase --> anaphase --> telophase

- when the cell is most radio-sensitive

interphase

- non-dividing period

- G1 = cell grows & synthesizes proteins

- S = DNA is copied

- G2 = cell grows & synthesizes proteins

prophase

- chromosomes shorten & thicken

- 23 PAIRS of chromosomes

- nucleolus disappears & nuclear envelope breaks down

- miotic spindle forms

- spindle fibers grab chromosomes to move them

- centrioles move to opposite poles

metaphase

chromosomes (each with 2 chromatids) align in the center of the cell

anaphase

chromatids from each chromosome separate & move to opposite poles

telophase

- cell divides organelles

- nuclear membrane forms around chromosomes

- cytoplasm divides

- cytokinesis = cell divides

meiosis

- cells divide twice in succession BUT chromosomes only duplicate once

- chromosomes reduced from 46 to 23

- 1 parent divides into 2 daughters (mitosis) THEN 2 new parents divide into 4 new daughters (each have 23 chromosomes)

DNA ladder

- purines = adenine & guanine

- pyrimidines = thymine & cytosine

- A pairs with T

- C pairs with G

chromosomes

- made of chromatin (chromatin is made of DNA & proteins)

- 2 sister chromatids connected by centromere

- contains genes

- responsible for directing cytoplasmic activity & transmitting hereditary info into the cell

telomeres

- protect the terminal ends of chromosomes

- arrays of TTAGGG repeats

- each time a somatic cell divides, telomeric DNA is lost

- 40-60 divisions shortens DNA considerably

- eventually will stop dividing (apoptosis) & tissue starts to age

- cancer & stem cells have telomerase to continue to lengthen telomeres (shortening telomeres is out body's natural anti-cancer mechanism)

DNA synthesis / replication

- occurs during interphase in the nucleus

- helicase = unwinds DNA

- DNA polymerase = runs down the separated strand to replicate the DNA

- primase = tells the DNA polymerase where to start

- ligase = bonds everything back together

- 2 replicated strands formed from 1 strand of DNA

RNA

- single stranded molecule that codes for proteins

- mRNA = messenger RNA

- rRNA = ribosomal RNA

- tRNA = transfer RNA (delivers amino acids)

DNA vs RNA

- single vs double stranded

- ribose vs deoxyribose

- uracil vs thymine

- RNA performs biologic functions vs DNA is just genetic code

protein synthesis steps

1. transcription

2. translation

transcription

- RNA polymerase unwinds section of DNA that codes for the protein of interest

- reads DNA to form mRNA (in nucleus)

translation

- mRNA travels outside the nucleus into the cytoplasm to find a ribosome

- rRNA assists with linking mRNA to the ribosome

- mRNA delivers the code to the tRNA (has amino acids attached)

radiation

- propagation of energy through space

- electromagnetic or particulate form

atom

- building blocks of matter

- smallest unit of an element that retains chemical properties

- atomic # (Z) = # of protons

- mass # (A) = # of protons + neutrons

- electrons in outer shells (bound to that shell by some amount of binding energy)

- electrons transition from higher to lower energy levels they release x-rays

charged particles

- lightly charged particles = electrons

- heavy charged particles = protons, alpha particles, carbon ions

uncharged particles

- photons = x-rays, gamma rays (electromagnetic)

- neutrons have no charge & only interact with nuclei (fast & thermal)

excitation

raising of an electron to a higher energy level without ejecting an electron

ionization

- radiation causes sufficient energy to eject 1+ orbital electrons from the atom

- electromagnetic or particulate

4 types photon of interactions

1. classical / coherent scatter

2. photoelectric

3. compton scatter

4. pair production

classical / coherent scatter

- energies below 10 KeV

- why the sky is blue

photoelectric

- diagnostic x-ray range

- photons with a high enough energy (keV) hit a higher Z material --> knock out inner shell electron

- characteristic x-ray released

- photon completely absorbed by electron

compton scatter

- higher energies (linear accelerator)

- high energy photon hits outer shell electron

- photon bounces off & gives away some energy --> freed electron & scattered photon

pair production

- high energy photon travels near the nucleus --> converted into an electron and positron (annihilation)

- photon energy is fully used to create the mass of the 2 particles (gives them all the energy)

- no scattered photon --> energy is used in annihilation

- threshold for annihilation = 1.02 MeV

ways to ionize matter

1. direct ionization

2. indirect ionization

direct ionization

- charged particles (electrons & protons)

- continuously interact with its surroundings along its path (directly interact)

indirect ionization

- uncharged particles (photons & neutrons)

- travels until it undergoes a single interaction --> charged particle created (causes multiple ionizations)

interactions of radiation

1. direct action

2. indirect action

direct action

- site of interaction = DNA

- ionizing radiation depositing energy directly in the DNA (causes damage at the site of the interaction)

- produces strand breaks, base damage, or DNA crosslinks

- more dominant in high LET particles (heavy = protons, neutrons, alpha particles)

- 30% of DNA damage

indirect action

- radiation ionizes water (or other molecules in the cell)

- produces free radicals (H, OH)

- radicals diffuse through the cell & interact with DNA

- more dominant in low LET particles (x-ray, electrons, neutrons)

- 70% of DNA damage

direct / indirect ionization vs direct / indirect action

- direct / indirect ionization = what type of radiation it is (physics)

- direct / indirect action = how the biological damage occurs once the radiation is in the tissue (biology)

single strand break

- 1 strand of DNA is damaged

- more common than double strand breaks

- sublethal (can be repaired) --> repair quickly & accurately

- rarely lethal on its own

- multiple single strand breaks close together on the same strand may not be repairable (can convert into double strand breaks)

double strand break

- both strands are broken within a few base pairs

- non repairable (may result in cell death, inability to reproduce, mutations)

- multiple single strand breaks = double strand break

- less common BUT more dangerous

- highly lethal --> most critical lesion responsible for radiation induced cell killing

strand breaks & delivery parameters

LET: more ionizations per path length = more breaks

- low LET: isolated ionizations = more single strand breaks

- high LET: more ionization in short distance = more double strand breaks

total dose: more dose = more ionization = more breaks

- low dose: less ionization = less common for single strand breaks to convert to double strand breaks

- high dose: more single strand breaks convert to double strand breaks

dose rate: more particle tracks at 1 time (particle density) = overwhelm repair mechanisms = more unrepairable breaks

- low dose rate: cells have time to repair single strand breaks before they accumulate to double strand breaks

- high dose rate: overwhelms the repair system = single strand breaks convert to double strand breaks

radiolysis

- ionization of H2O --> breaks water into hydrogen & oxygen

- dissociation of molecules by ionizing radiation

after radiolysis

- recombine into H2O (no damage)

- join with another water molecule (potential for damage)

- ion radicals are unstable & have a short lifetime --> decay to form free radicals

- free radicals are not charged but have an unpaired electron (reactive)

free radical

- contains an unpaired electron in the outer shell (highly reactive)

- most common free radical = hydroxide (OH-)

hydrogen peroxide (H2O2)

toxic to cells (can damage DNA)

charged particles tracks

- paths in matter differ between lightly charged (electrons) & heavy charged (protons) particles

- electrons = random paths with multiple scattering events

- protons = dense linear ionizing track

path length vs range

- path length = distance the particle travels

- range = the depth of penetration of a particle in matter

THE SAME FOR HEAVY PARTICLES

specific ionization

- ion pairs produced per unit path length

- expressed in ion pairs

- as heavier particles slow, specific ionization increases to a maximum (bragg peak)

radiosensitivity

- degree to which a cell, tissue, organ, organism is susceptible to the damaging effects of radiation

- variables = age, sex, tissue type, radiation type, rate of exposure

- radiation type = 10 mGy alpha > 10 mGy x-ray (alpha deposits energy into 1 concentrated area)

- rate of exposure = exposed over a shorter time period causes more damage (cells have less time to heal)

linear energy transfer (LET)

- average amount of energy deposited per unit path length

- high charge (beta, alpha, protons) & high mass = high LET

- high energy = low LET (likely to travel further without interaction)

- directly ionizing radiation = effective LET is determined by particle itself

- indirectly ionizing radiation = photons don't deposit energy directly (interact with matter to release secondary electrons) —> electron track determines the effective LET

- deposits energy in a shorter distance = more concentrated damage & higher potential for biologic damage

- high LET = high biologic effectiveness

- high LET (alpha & neutrons) are densely ionizing & have greater chance of interaction BUT they loose energy rapidly (can only penetrate a short distance)

- low LET (x-ray & gamma ray) are sparsely ionizing & have a decreased chance of interaction (deposit energy in a long distance

dose

- the amount of radiation

- expressed in absorbed dose

- measure of the energy absorbed per unit mass of tissue

- as the total dose of radiation is increased, the # of tracks will increase

- more than 1 track of low LET radiation may go through a target, increasing the chance of damaging the DNA

relative biologic effectiveness (RBE)

- radiations ability (effectiveness) in causing biological damage

- equal doses of different types of radiation don't produce equal biologic effects

- x-rays are used as the standard (250 keV) --> RBE of 5 does 5x more damage than 250 keV x-ray)

- how we compare the effectiveness of different types of radiation

- more damage = high RBE

- tells us how "potent" a type of radiation with some energy is at damaging living tissue compared to standard x-rays

- high LET = high RBE

- varies with energy, dose rate, LET, dose

RBE & LET

- high LET = more effective radiation = kills more cells (increase dose = less cells survive)

- LET increases --> RBE increases slowly then suddenly reaches a peak of 100 keV/um (optimal range because this is where the average separation of ionizations coincides with the diameter of DNA, causing double strand breaks)

cell changes

3 things occur with the creation of ion & free radicals

1. cells can recombine (no damage to DNA)

2. cells can join with other free radicals & make new molecules

3. cells can react & damage the DNA target (cause a biological effect / cell damage)

target theory

- cell death is caused by the inactivation of specific targets within the cell

- there are specific numbers of targets that must be hit to kill the cell

- if all the targets aren't hit --> the cell has a chance to survive & repair the damage

DNA damage

- abnormal chemical change (most will repair)

- unrepaired damage in nondividing cells accumulate --> cause aging in brain & muscles

DNA mutations

- random

- permanent changes in the DNA (stemming from errors in repair of DNA damage)

- change in a base pair

- can progress to cancer

- 2 classes = point & chromosomal

point mutations

- changes in single nucleotides

- most will repair

- substitution, insertion, deletion

point mutations: deletion

the loss of a nucleotide

point mutations: insertion

addition of a new nucleotide (shift and different protein)

point mutations: substitution

different nucleotide is substituted (different protein)

effects of point mutations

- silent mutation

- missense mutation

- nonsense mutation

- frameshift mutation

frameshift mutation

leads to a significant loss of function & energy amino acid following will be altered (changes following amino acids)

nonsense mutation

creates a premature stop codon

missense mutation

results in a single different amino acid

silent mutation

results in the same amino acid generated

chromosomal mutations

large segments of chromosomes are altered

aberrations

- when radiation strikes the DNA, part of the chromosome / chromatid may break off

- the broken end appears to be sticky & can rejoin with other broken ends

- chromosome vs chromatid

chromosome aberrations

- result if a cell is irradiated BEFORE chromosome duplication

- produces a single strand break on the chromatin

- cells will undergo replication & both daughter cells will have a damaged chromatid

chromatid aberrations

- result if cell is irradiated AFTER DNA synthesis

- may produce a single / double strand break on the chromatin (not within daughter cells)

3 nonlethal results of aberration

1. restitution (chromosome OR chromatid)

2. translocation (chromosome OR chromatid)

3. deletion (chromosome OR chromatid)

restitution

- the broken ends of the chromosome could rejoin with the same chromosome (everything remains normal for the next mitosis)

- considered complete repair of the chromosome

translocation

- a segment of a chromosome breaks off & attaches to another chromosome

- depending on the info transferred, the chromosome may not function normally (cell may be able to live)

- often associated with several human malignancies

- in germ cells --> can be passed on to future generations

deletion

- removes a chromosomal segment

- the break doesn't repair --> next mitosis the genetic info is lost

- acentric fragment = without a centromere (won't be replicated because without a centromere the chromosome can't be split)

when does DNA replication occur in the cell cycle?

interphase (S phase)

what part of the cell makes proteins?

ribosomes

cell organelles are located in the ________ of the cell

cytoplasm

if a cell is to divide, when do the organelles (centrioles) duplicate?

telophase / cytokinesis

where does mRNA travel after transcription?

to a ribosome in the cytoplasm

what particle is most likely to interact with DNA in photon irradiation?

RH free radical

the most important target of the cell is _______

DNA

what is a gene?

segment of DNA that codes for a protein

what does adenine pair with?

thymine

what chemical composition will be the most damaging to a cell?

OH free radical