Final Exam HPS 420 *use

Describe Giemsa staining

binds to adenine thymine nucleus

quick and easy

Describe G banding

Stained w/ Giemsa

makes defined banding pattern

specific to each chromosome

time consuming needs an expert lots of info

What is standard fish

1-3 chromosoei’s are painted with counter stained w/ dna stain DAPI

Describe m Fish

allows for each chromosomes to be painted w/ a specific color

Describe m band

a single chromosome to be painted w/ bands for specific segments of the chromosome

Describe α in the α/β ratio

linear w/ dose

lethal dmg

high let

cannot be repaired

complex clustered

Describe β in the α/β ratio

quadratic var w/ dose

dmg can be repaired

low let

Describe α/β ratio

the cell killings are they are both =

Describe what happens in low α/β ratio biological effect wise

increasing the dose per fraction significantly increases the biological damage

Describe what happens in high α/β ratio biological effect wise

These are more "linear" in their response

what is extrapolation (n) in the survival curve

quesstimate of width of the shoulders

describe the Quasi threshold (Dq )

almost a threshold dose, dose below which rad. purportedly has no effect

Describe the initial slope (D1)

resulting from a single gene event killing

Describe the final slope (Do)

resulting from multiple event killing

dose that reduces survival to e- (37% of the previous val)

Describe SF2

Surviving fraction after 2 Gy in cancer therapy fractions of 2 Gy often used

What does the shoulder mean bio wise

assuming more than one hit is needed to kill a cell

What does a steep slope mean?

Cell survival drops quickly w/ small increase w/ dose

very rad sens

what does the shallow slope mean

cell survival decreases with dose

slower cell killing

low killing

better survival

Why do we need a plating efficiency?

to tell us how many cells can successfully grow into colonies

what is the platting efficiency definition?

the % of untreated cells seeded grow into colonies

what is the formula of the platting efficiency

number of colonies/number of cells plated

In the Linear Quadratic model describe α

Linear

no shoulder

One hit

Low dose

In the Linear Quadratic model describe β

creates sub lesion that interact (misjoin → lethal)

shoulder

high dose

What are the different cell killings

bystander effect

apoptosis

mitotic

autophagic

senescene

describe the bystander effect

effects occur with gap junctions

effects can be transferred thru med

one cell that is bad can effect the other cells that were once healthy

Describe apoptosis

programmed death

cell shrinks, membrane blebs, fragmentation occurs

Describe mitotic

most common

cells die when they try to divide

describe autophagic

self digestive via lysomal degrad.

describe senescene

irreversible cell cycle arrest

alive but cannot divide

List the cell cycle from most sens to resistant

M → G2 →G1 → S

What can happen if that are mutations in genes

they are senstive to cell killing, the cell fail to verify dna, may start mitosis, cannot repair SLD

what could happen if there is a mutation in regulatory proteins

Mutation here ensures that damaged DNA is passed on or results in immediate mitotic death.

list some cell cycle repair proteins

ATM

BRACA 1 / BRACA 2

P53

DNA- PCKS

Describe ATM

sensor protein that detects DSBs and triggers cell cycle checkpoint

Describe BRACA 1/BRACA 2

HR repair

Describe P53

Guardian of genome

triggers G1 arrest/apoptosis

Describe DNA -PCKS

NHEJ

Describe OER

It is dose dependent

Low at HIGH LET

High at LOW LET b/c there are free radicals that are available

Describe HIGH let and their dependence

Less dependent

b/c it is densely ionizing and creates complex irreparable double stand breaks no matter what cell cycle they are at

Describe LOW let and their dependence

More dependent b/c it is sparely ionizing allowing the cell to die based off of more factors

how can fractionation affect the bio outcome

gives time for the cell to repair

Describe the different cell cycles

G1- The cell increases in size, produces RNA, and synthesizes proteins necessary for DNA replication.

S- DNA replication occurs. The cell copies its entire genome so each daughter cell will have a complete set of chromosomes.

G2-The cell continues to grow, produces proteins, and reorganizes its contents to prepare for mitosis.

M-The division of the nucleus, divided into prophase, metaphase, anaphase, and telophase.

What are the classifications of radiation damage

lethal dmg

potentially lethal dmg

sublethal dmg

Describe lethal dmg

cell death

describe potentially lethal dmg

Radiation dmg can be mod by post irrad. environmental conditions

describe sublethal dmg

dmg under conditions can be repaired unless more SLD is added = lethal

What was the Elkind experiment

We saw the SLD repair

increase cell survival

Dip b/c re assortment

We see: Repair, reassortment, repopulation

What are the 4 Rs of radiology

Repair

Reoxygenation

Reassortment

Repopulation

Describe Repair

Repair of SLD

fractionation increase repair

Describe re population

Increasing cell survival b/c of the division, we irrad before the tumor has a chance to repopulate to make sure it won’t come back

fractionation INCREASES this

Describe re assortment

the cell position influences the sens

fractionation allows for cells to move from S→G2/M

What is the dose rate effect

caused by sld repair

small shoulder = modest dose rate effect

lg shoulder= greater dose rate effect

In the dose rate effect, what are we comparing

low doses vs high doses that create the same bio. effectiveness

Describe BIG DRE

A lg difference

cells live better and is spread out over time

Describe smll DRE

little difference

What are the effects of fractionation

allows for an increase in total dose to be delivered
spreading out allows for the atom to repair ? repopulation

What is the inverse dose rate effect

where low doses increase cell death

What happens in the inverse dose rate effect

occurs in very very low loses, the low doses allow for the cells to move thru the cell cycle, the g2 block occurs, they accumulate there and then rad. kills em

What is Brachytherapy

rad therapy using sealed rad materials

important for clinical application

What are some of the Brachytherapy

intracavity

interstitial

surface

intraluminal

intraop

intravascular

In brachytherapy describe LDR

temp

1-4 days

Dr = ~50 gy/hr

uterine cervix

IR92

in brachytherapy describe HDR

becomes prefeed

3-12 fractions

few mins

in brachytherapy describe perma

short ½ times

increase dr

iodine -125

Define OER

the ratio of hypoxic cells to aerobic needed to achieve the same bio effect

what is the formula

hypoxic/areobic

what is the oxygen fixation hypoxia

indirect dmg, the dmg can be repaired under hypoxia but the dmg is perma

what are the steps for oxygen fixation hypothesis

1) high energy electrons created by x ray photon

2) creates an OH radical

3) releases a proton

4) oxygen? peroxyl radical is made and fixed the dna

Sens cells = _____ OER

Low

Resistant cells = ___ OER

High

Define chronic hypoxia

limited diffusion distance of oxygen repairing tissue

Describe chronic hypoxia

cells closest to the capillaries get more oxygen

cells farthest from capillaries receive less oxygen

makes up a continuum of oxygen concentrations

describe acute hyoxia

temp closing/blockage of a blood vessel

vessel open/close at random times

temp. hypoxic cells

Where does OER and LET reach unitiy

100-200 Kev/um

Where does OER drop?

60 kev/um

Describe S phase’s OER

2.8-2.9

Describe g1’s OER

2.3-2.4

Why does S phase need more OER than the other phases?

Because cells are resistant here and needed MORE oxygen

Define LET

The amt of energy imparted to the medium by a charged particle per unit length of track Kev/um

What does LET depend on?

energy of rad

type of rad

type of material

What is the formula for LET

△E/△X

What is low let

induces radicals more sparsely within a cell

what is high let

deposits a large amt of energy in a small distance causing dense ionization along a track

What are the two ways to calculate LET

track avg

energy avg

Describe track avg

divides into equal lengths then calculate the energy deposited in each length and find the mean

describe energy avg

divides the track into equal energy increments and avg the lengths of tracks over within these energy isancrements are deposited

Define Relative bio effect (RBE)

The RBE is a raito of test rad. compared w/ gamma rays/ 250 KeV x rays that makes the same bio effect

What is the formula for RBE

dose in gy of y rays/dose in gy test rad. source

What effects RBE?

LET

Rad dose

number of fractions

dose rate

bio system/end point

Why is RBE higher at low doses?

b/c rbe gets larger with low dose due to the shoulder effect and that we can see repair

What is the relationship with OER/LET/RBE

LET: Increases

RBE: Increases

OER: Decreases

What are the stages of ARS?

Prodromal syndrome → latent → manifest illness → recovery death

What are some of the acute rad syndromes

cerebrovascular syndrome

gastrointestinal syndrome

hematopoietic syndrome

hematopoietic syndrome

Symptoms?

Time of death

Underlying cause?

dose range

Symptoms: low number of lymphocytes/other blood cells, infections, fever

Time of death: 30-60 days

Underlying cause: active stems are killed by rad, can recover

Dose Range: 2.5-5 gy

gastrointestinal syndrome

Symptoms?

Time of death

Underlying cause?

dose range

Symptoms: nausea/vomiting, prolonged diarrhea, dehydration, loss of appetite, weight loss/emaciation:

Time of death: 3-10 days

Underlying cause: depop. of the epithelial lining, stem cells are restricted to crypts of small intestines

dose range: >/= 10 gy

cerebrovascular syndrome

Symptoms?

Time of death

Underlying cause?

dose range

Symptoms: disorientation, loss of coordination of muscular movement, coma, convulsive seizers

Time of death: 30-50 hrs

Underlying cause: change of permeability of small blood vessels in the brain, dmg to microvasculature

dose range: 100 gy

Describe Stochastic effects

no threshold

Severity is independent of dose

probability of occurrence increases w/ dose

Cell alive just modded

ex: cancer

Describe determinstic

has a threshold

cell dies

aka tissues reactions

severity increases w/ dose

ex: erythema, cataracts, nausea

What is the latent period of carcinogenesis

The time between initial exposure vs clinical diagnoses

What are the latent periods for leukemia

shortest

5-15 yrs

what are the latent period of solid tumors

longest

10-60 yrs