Lecture 10 Flashcards
radiation biology
study of the biological effect of ionizing radiation on tissue
biological effects of radiation
stochastic effects and deterministic which is acute
stochastic effects
late effects: cancer and hereditary
what does the probability and severity do with stochastic dose effects
probability increases with dose, but severity is independent of dose
deteministic effects
acute effects: erythema, cataracts, blood cell defects, acute radiation syndrome
what does the probability and severity do with deterministic dose effects
severity increases with dose, but probability is independent of dose
what is the most common way to get deterministic and what is the most common way to get stochaistic
deterministic-is from occupational, but there is not very often. Diagnostic X-rays are the most common for stochastic. There is a threshold for the deterministic effects
how does ionizing radiation deposit energy
excitation, ionization, thermal heating- largest but very small component
what produces chemical changes in the tissue
excitation and ionization, which produce biological effects
what are biological effects of radiation
delayed after a period of time
can you tell the difference between chemical or physical agents
no
what is the direct effect of radiation on the tissue
photon directly ionizes or excites a DNA molecule, which then DN< RNA< protein or enzyme is then ionized or excited
what is the indirect effect of radiation on the tissue
a reactive chemical is produced, which interacts with water and the majority of tissue is water. This produces free radiacals, which have an unpaired electron, so they are very reactive.
what can ROS form
water, which does nothing or it can form a hydrogen peroxide which is damaging to interact with macromolecules
what enhances ROS damage
O2
what predicts the severity of biological response
the cell function that is affected especially the cell division
what happens to cells with the most damage
they apoptosis, and eliminate future biological response
what is target theory
model of cell damage. a cell may be inactivated by a certain number of hits. A hit may be direct or indirect interaction. Cells have certain DNA that is not redundant. A hit to redundant molecules will not result in cell death
is dingle strange or double stranded breaks more common and what are they
single are more common and they are more easily repaired. The double stranded happen less frequently but are harder to repair
what two things can cause a mutation
base deletion or substitution
what happens to chromosomes when hit with radation
broken ends are sticky and and can rejoin with other broken ends, and this repair can lead to a whole mess
can lead to eccentric or miscombined with different translocations.
what are the aberrations present with the chromosomes
dicentric, acentric, ring
what can be used to estimate the amount of radiation received
the number of aberrations in human lymphocytes can be used to estimate the amount of radiation exposure received. Total body doses>.25gy can be detected many years later
cell radiosensitivity
used to evaluate the effect of radiation on cell proliferation under various conditions including different types of ration, environmental factors, different types of cells. Cells are grown in tissue culture the exposed to radiation then surviving colonies are counted. Cell survival curve shows fraction surviving versus dose
what is n
it is the extrapolation number between n2-10 and the number of hits required to inactivate cell or the number or critical targets in a cell
what is D0
1/slope indicates the general radio sensitivity of cells
what is a large D0 mean
it means there is a radioresistance
low D0 means what
radiosensistive
D0 is usually between
1-2 gy
Dq
threshold dose- width of the shoulder region. Measures ability of cells to recover from sublethal damage.
what is large Dq
cells can easily recover or low energy radiation
what factors effect the radio sensitivity of cells
dose rate, dose fractionation, radiation quality, oxygen, chemical protectiors, type of cell, stage of the cell cycle
dose rate and fractionantion
high dose rates cause greater amage. Fractionation of dose reduces the biological damage. Low dose rates and fractionation gives the cells time to reapiar
LET
linear energy transfer. high LET is alpha protons and high energy photons. Low LET means there is beta stuff and gamma rays
dose low or high LET cause more damage
high
does free O2 increase or decrease damage
increased cell damaged because there can be formation of products.
what do chemical protectors do
decrease cell damage and these chemicals scavenge free radiacls and add an H to help DNA repair like sulhydrl amifostine, but almost need it to be toxic
which cells have the greatest sensitivity
rpid devision, large number or future divisions, low differentiation, lymphocytes are radio resistant, but still kinda radiosensitive
what cell cycle is most sensitivie
during M and late G2 phase
what cell cycle phase is most resistant
late S phase
what happens if the parenchyma is radioresistant
damages first occurs in the vasculartue so later effects of blood flow
if the parenchyma is radiosensative
quick damage
what are some radiosensitive organs
skin, reproductive organs, eye, hematopoietic cells, GI, CNS
radiation effect on the skin what is the threshold
1-2. Early effects are erythema, inflammation, dry desquamation, most desquamation. late atrophy, fibrosis, changes in pigmentation, necrosis, ulcers, cancer.there are some changes like loss of chair, sweat and sebum. Eraly hits the epidermis while late is the dermis
2-6gy to skin
erythema and temproary hair loss
6-10 to skin
more erythema
15 to skin
severe erythema and dry desquamation
20-50 to skin
intense erythema, acute radiation dermatitis, moist desquamation, edema, dermal hypoplasia, vascular damage, permanent epilation, permanent pigment changes
above 50 to skin
ulceration and necrosis
radiation effects to gonads
2.5 is sterility for temporary and 5gy is permanent- spermatogenesis is most sensitive
female gonad effects
intermediate follicles, 1.5 gy temporary and 6 is permanent. exams are rare over 50
radiation effects to eye
lens because cannot remove damages- shorter for high doses but usually over a uear
what is there threshold dose for the eye
2-7 old new .5. protracted 4 gy over 2 months or 5.5 gy over 4months.
how much dose a head CT give
50mGy to eye
acute radiation syndrome
large acute radiation exposure to the whole body. Combination of 3 syndromes, hematopeotic, GI, neuro, and chernobyl causes 30 cases or it
prodome ARS
anorexia, nausea, vomiting, diarrhea- up to 6 hours
latent ARS
no symptoms for up to 4 weeks
manifest ARS
4-6 weeks prodrome plus organ damage
recover or death
after 6 weeks
hematopeotic sundrome
stem cells in bone marrow-
.5-1 in heme
decrease CBC
<2 in heme
generally recoverable
2 in heme
die in six weeks with no treatment
> 8gy heme
wil die without treatment in 1-2 weeks without BMT
GI sundrome
crypt cells are hit and no longer reproduce. damage to intestinal lining
what is the GI dose range
10 is the threshold and above 12 is fatal within 5-12 dyas
what is the neuromuscular effect and threhold
50 and it is rate and will occur within 2-5 days from cardiovascular shock
what is the range of developing leukemia
2-3 years
what is the latency for solid tumors
more than 40 years
why is it difficult to study radiation induced cancer
cancer incidence is high in the population
what was the mean dose from the atomic bomb
200 mSv
what is the dose for an abdomen CT affecting BMT
5mgy
in AK treatment
see increased leukemia incidence
what happened with the mastitis patients
increased doses lead to increased breast cancers
what happened with the radium girls
osteogenic sarcoma- threshold of 5gy of radium. high LET from Ra226 and 228 and this is 100 times the population
how does the dose data stack up for cancer
more data for high dose exposures but it is insufficient for lower doses. Use dose response to predict the lower ones
what is the formula for the dose response curve
it is R=aD+BD2 and it is not linear because linear overestimates the indicence
what are the pitfalls of the non threshold model for dose response
it estimates a higher cancer incidence at lowe doses compared to threshold model
what are the pitfalls of the non threshold linear model for dose response
more likely to overestimate at low doses ,but it is the best for conservative model, but it cannot predict excess cancers from this model
relative risk method
ratio of cancer indcidence in the exposed group relative to general population. excess RR is 1-RR
absolute risk
number of excess ration induced cancers that occur in an exposed population for specific dose per year
Beir V report
exposure to low levels of ionizing radiation. contains the cancer incidence estimates from a panel of experts
cancer mortality risks from BEIR
8% per Sv adult workers and high dose/dose rates. Dose and dose rate effectiveness
what is the best model for leukemia and bone cancer
linear quadratic model
what is the most frequent radiation induced cancer
leukemia and it has low incidence otherwise. children have 2-3 year latency, >45 8-10 hear latency. linear quadrative
what is the absolute lifetime risk for leukemia
1% per Sv exposure
what is the second most common radiation cancer
thryid females are at higher risk. Latent for 5-35 years. Mortality is low though
what is the latent period of breast cancer
10-40 years and long period of expression. Risk increases with age
what were the hereditary results from radiation in flies and mice
radiation cuases mutations, and not different from spontaneous mutations
what happened with human sutdies
no increase in genetic effect above spontaneous
what is the genetically significant dose
does expected to produce the same genetic effect to the entire population as the actual dose received by a specific group. GSD is used to evaluate the magintude of the effect of certain exposure. Depends on gondola dose and expected offspring
what are the effects of radiation to the conceptus
congential abnormaltities, growth retardation, reduced IQ, increased cancer risk, but dependent on the stage
what is the effect at the preimplantation stage
all of nothing. prenatal death or repair and replacement of damaged cells will occur.
what is the threshold dose at primimplantation
50-100 or 250 after implantation
when is organogenedid 2-8 weeks
it is the most critical because of the changes to organs. this is at 100-200
fetal growth stage
8 to birth- nervous and sensory organs can be affected, but reduced IQ or behavioral, but there are less major malformations.
micorcephaly
small heads
mental retardation
seen in ecvess
what is the most common time that in utero radiation would cause cancer
doses as low as 10mgy can cause it with the 3rd trimester being the most sensitive, but it is controversial
what test has the highest in utero dose
CT
most exams for diagnosis
do not get above 100 so there is usually not much effect
