• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/150

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

150 Cards in this Set

  • Front
  • Back
What is comparative genomic hybridization
1. Tumour DNA harvested
2. Reference DNA harvested
3. DNA cleaved
4. DNA amplified and labelled with fluorescent probe (red - tumour and green - control)
5. Two samples mixed and hybrized in DNA microarray
6. Ratio of red to green socre to measure loss or amplicfication of genes (should be approximately equal unless overexpressed or underexpressed)
What is the mechanism of action of Mitomycin C? What is its interaction with RT?
Mitomycin C inhibits RNA and DNA synthesis
It is converted in vivo to a bifunctional or trifunctional alkylating agent
Activity is more toxic to hypoxic than to aerated cells
It is strongly synergistic.
Main SE is myelosuppression
What is the action of 5FU?
Anti-metabolite. Structural analogue of thymdine. Main mechanisms of action is to inhbit thymidylate synthetase. Moderate synergy with radiation.
What is trastuzumab?
humanized monoclonal antibody which targets the extracellular domain of the HER-2 (erb-b2) receptor (of the EGFR receptor family group).
It prevents dimerization of the receptors and thus prevents the intracellular tyrosine kinase activity, preventing progrowth signalling cascade to the nucleus.
In vivo, the mechanism of cell kill may be from decreased proliferating signalling. Immune mechanisms have also been suggested.
Define Tpot
Potential doubling time is the doubling time, taking into consideration the growth fraction and the cell cycle length, but not cell loss
Tpot = (lambda) x Ts/LI
Define Cell Loss Factor
Cell loss factor is the rate of cells loss from a tumour as a proportion of the rate at which cells are being added to the tumour by mitosis.
CLF = 1 - Tpot/Td
What are the average GF and CLF for animal tumours?
GF: 30-50% (intially higher)
CLF: Steel - 77%
What are the types of radiosensitisers?
Halogenated pyrimidines
Nitroimidazoles (misonidazole, etanidazole, nimorazole)
How do nitroimidazoles work?
electron affinity of the nitroimidazole determines its effectiveness at radiosensitising. It must be able to be highly soluble in water and lipids and diffuse a considerable distance, and no be subject to rapid breakdown. It should preferentially sensitise hypoxic cells.
What the groups of hypoxic cell cytotoxins?
1. Quinolone antibiotics (mitomycin C)
2. Nitroaromatic compounds
3. Benzotriazine di-N-oxides (tirapazamine)
How does tirapazamine work?
Tirapazamine is a bioreductive agent that has a hypoxic/oxic cytotoxicity ratio of ~100.
It is activated by cytochrome P450.
In vitro the cytotoxicity is greater than additive for the hypoxic cells
Broadly what are the three types of interactions between chemotherapy and radiotherapy?
1. Spatial cooperation
2. Indepedent cell kill
3. Molecular and cellular interactions (i.e. synergyantagonism)
What are the 5 types of cellular/molecular interactions between chemotherapy and radiotherapy? Give an example of each.
1. Impaired DNA synthesis/repair (5-FU, cisplatin)
2. Increased apoptosis (antimetabolites i.e. gemcitacine)
3. Cell cycle synchronization (gemcitabine)
4. Reoxygenation (taxanes)
5. Inhibition of cellular proliferation (Most likely mechanism i.e. any with advantage of chemo addition)
What chemotherapeutic agents have strong interaction with RT?
Dacarbazine (alkylator)
Bleomycin, dactinomycin, mitomycin C, doxorubicin/adriamycin (antibiotics)
Gemcitabine (antimetabolite)
Cetuximab (targetted)
What chemotherapeutic agents have intermediate interaction with RT?
Cisplatin (atypical alkylator)
5FU, capecitibine (antimetabolite)
What chemotherapeutic agents have weak interaction with RT?
carmustine, lomustine (alkylators)
Methotrexate, hyrdoxyurea (antimetabolites)
Paclitaxel (weak
How does cisplatin work?
binds to DNA forming intra and interstrand crosslinks (intermediate synergy)
How does mitomycin C work?
Mitomycin C is a prodrug that in vivo is converted to a bi- or tri-functional alkylator (strong interaction), Major toxicity is myelosuppression.
How does bleomycin work?
Binds to DNA to inhibit synthesis of DNA, RNA and proteins. Causes single stranded break (strong interaction).
How does doxorubicin/adriamycin work?
Complex. Binds to DNA, intercalating, and causes inhibition of DNA topoisomerase II (strong interaction). Major toxicity is cardiac, recall skin reactions.
How does 5FU work?
Inhibits thymidylate synthetase. Major toxicity is GI. (intermediate interaction)
How does capecitabine work?
Oral prodrug that is converted to 5FU. It inhibits thymidylate synthetase (intermediate interaction)
How does hydroxyurea work?
Inhibits nucleotide reductase (converts nucleotide to deoxynucleotide). (weak interaction). Myelosuppresion is major toxicity.
How does methotrexate work?
Inhibits dihydrofolate reductase. Inhibiting synthesis of thymidine and purines (Guanine and adenine)
How does gemcitabine work?
Antimetabolite. Nuceloside analogue. Inhibits DNA synthesis. Strong interaction
How do taxanes work?
Taxanes stabilise the microtubule structure of the mitotic spindle, but does not allow completion of mitosis as the cells are unable to disassociate from the spindle. (paclitaxel weak interaction)
How do vinca alkaloids work?
Prevent polymerization of the microtubules necessary for the mitotic spindle.
How does cetuximab work?
Cetuximab is a recombinant human/mouse chimeric monoclonal antibody which binds to EGFR, preventing dimerization and activation of receptor kinases, and hence pro growth signals to the cell nucleus
What is poisson statistics and its relevance to cell survival?
Radiation cell kill is a random event
Number of tumours or cells killed follows a probability distribution known as a Poisson distribution (where if the average number of surviving clonogens is 0.5 over 100 tumours, then not all tumours will share this result - there will be a statistical range of values)
When describing TCP it is the probability of zero clonogens that is of interest, which is the zero order term of the poisson distribution.
If lambda is the average number of clonogens per tumour after irradiation, then TCP = e (-lambda)
If the average number of suriviving cells per tumour is a negative eponential function of dose, then the characteristic sigmoid dose response curve is obtained
NB this will be influenced by biological and dosimetry heterogeneity and this model cannot be regarded as some intrinsic biological property of the tumour
What may affect the steepness of the dose response curve?
Oxygen
LET of radiation
Inherent radiosensitivity
Dose Rate
What is the gamma factor?
Gamma factor is a term which describes the change in dose response in the steep part of the sigmoid curve. It describes the increase in cell kill for 1% increase in dose.
What is the single target-single hit model of inactivation?
single target-single hit model describes the hypothesis that only a single sensitive target would need to be inactivated to lead to cell death.
This would be described by a exponential relationship i.e. a sraight line on a semi log plot.
This type of response may be seen with very radiosensitive cells and also at very low dose rates, and in high LET radiations
What is the single hit, multitarget model?
This is the hypothesis that for cell kill there are number of critical targets in the cell, all of which require inactivation to kill the cell.
Cell survival is given by:
S= 1- [1 - exp (D/D0)n
Only one hit to a number of sensitive targets is required
Poisson statistics may be applied
This relationship shows a shoulder on a cell survival curve, whose size can be indicated by the quasithreshold dose.
What is radioresponsiveness?
A general term to describe the overall clinical response to radiotherapy
What is radiocurability?
Radiocurability refers to hte direct effect of radiation on the tumour at the primary or regional site and does not necessarily equate with patients cure from cancer.
What is radiosensitivity?
radiosensitivty is a measured response describing the degree and speed of regression during and immediately after radiotherapy. For most tumours there is no significant correlation between responsiveness and radiocurability.
Define SF2.
Surviving fraction at 2Gy.
What is a functional sub unit?
a functional subunit is the largest volume or unit of cells that can be regenerated from a single clonogenic cell.
What is the tumour bed effect?
The TBE is the slower rate of tumour growth after irradiation as a result of injury in the irradiated vascular bed
What part of the cell cycle is most senstive to OER?
S most sensitive
G1
G2/M least sensitive

i.e. opposite order to general radiosensitivity to radiation.
What is the general value of OER?
Low LET - 2.5-3.5
Neutrons 1.6
High LET - 1.0 (i.e. no effect)
Describe how and the time course of indirect DNA damage caused by Ionizing radiation
photon
fast electron
ion raidcal (10 exp-10)
free radical (10 exp-9)
Chemical Changes
Biological effects (weeks - years)
Define OER.
OER is the ratio of dose in anoxic conditions to the dose in oxic conditions to produce the same biological endpoint.
when does oxygen need to present?
At or very closely following RT (within 5ms)
What is the diffusion distance?
70 micrometers
What concentration of oxygen is required?
3mmHg or 0.5%
(NB venous concentration is 20-40mmHg). No improvement above 2%
What is the significance of hypoxia?
1. decreased sensitivity to RT
2. tumour hypoxia has been correlated at certain subsites to poor outcome
3. May mediate tumour behavour - positive selection, cause adaption, influence DNA repair
4. May mediate disease progression i.e. growth factors (HIF) and gene instability
List techniques to measure hypoxia
1. Eppendorf probes
2. Non invasive imaging (18F-Miso)
3. Endogenous hypoxia markers
4. Nitroimiazole markers (injected prior to biopsy)
What is the human evidence for importance hypoxia?
Cervix
Sarcoma
How does fractionation affect hypoxia?
Proportion of hypoxic cells is believed to stay relatively stable during treatment i.e. the radioresistant suriving clonogens reoxygenate to a similar level as prior to first fraction (has been estimated in some sites as 15% - although there is NO human evidence that this occurs it is suspected by the high rates of cure at 60Gy in tumours known to be hypoxic)
How does hyperthermia work?
Believed to be by protein denaturing, although there is a change in slope at 43 degrees and it is postulated that there may be two different mechanisms above and below this point
What part of the cell cycle is most sensitive to RT?
S phase (? protein synthesis is very high in this part)
G0/1 less sensitive
What other factors after sensitivity to heat?
increased in low pH (although chronic low pH may protect cell)
Increased sensitivity in nutrient deprived areas
How do cells die from heat exposure?
apoptosis
What is thermotolerance?
thermotolerance is the induced resistance to a second heat exposure by prior heating
What are the kinetics of thermotolerance?
It may develop to a maximum in 1-2 days and decay slowly over a 1-2 week period.
What is the believed mechanism of thermotolerance?
May be mediated by heat shock proteins.
How does and heat and radiation interact
Independent but additive as complementary patterns of senstivities (i.e. cell cycle, pH, oxygenation)
Interaction between heat and RT may cause sensitsation by inhibiting repair of DNA
What are the main factors which determine acute effects?
Dose
Overall treatment time
Fraction size (but less imporant than for late effects)
How does amifostine work as a radioprotector?
Radical scavenger?
Name three methods of augmentation of late effects?
1. Radical scavenging i.e. amifostine, selenium
2. Gene therapy i.e. superoxide dismutase
3. Growth Factors
4. Moduclation of macrophage activity
What effect do growth factors have on late effects?
- haemopoetic grwoth factors have not been shown with systemic administration to reduce mucositis
2. Keratinocyte grwoth factor has been shown in animal models to ameliorate skin, mucosa, intestine, lung and bladder effects
3. A treatment against TGF-beta has prevented fibrosis in mice
4. TNF singalling. TNF blocking in mice actually increased radiation nephropahty
What are the 4 phases of radiation syndromes?
Prodromal
CNS
GI
haematological
Describe the prodromal phase of TBI?
Symptoms begin and last til onset of secondary syndrome
Time to onset, severity and duration is proportion is dose received
2 main groups of effects
1. GIT
- vomiting, diarrhoea, anorexia
2. Neuromuscular
- headaches, fevers, seating, cramps, hypotension
NB immediate diarrhoea, fever and hypotension indicate a supralethal dose
Describe the cerebrovascular syndrome?
Occurs at ~100Gy gamma radiation
Death within 24-48 hours
Symptoms
- onset within minutes
- nausea/vomiting/diarrhoea
- respiratory distreations
- seizures
Not solely atributable to brain only as higher doses are required for brain only death, vessel permeability is postulated as a potential cause
Define the gastrointestinal syndrome.
Occurs at >10Gy.
Death occurs at 3-10 days post exposure.
Symptoms
- nausea/vomiting
- diarrhoea
- lethargy
Depopulation of the GIT tracts resulting in sterilisation of the stem cell compartment but not the fuctional compartment, which as they die and are sloughed as their natural caouse they are not replaced leaving a denuded surface resulting in bacterial growth and entryk
Define the haemopoeitic syndrome.
occurs at 2.5-5Gy.
Peak death at 30 days but measured up to 60 (i.e. LD50/60)
Very old and very young most sensitive
Mitotically acitve precursor cells in teh bone marrow are sterilised with subsequent mature cells - platelets, WBC's and RBC's diminishing as they approach their nomral half life but are not replaced by the marrow.
Ater 3 weeks:
- chills, fivers, fatigue, petechial hameorrhages, ucleration of mouth and epilation of skin
- hameorrhages
- RBC loss does not usually occur as half life in order of 120 days
- NB lymphocytes will disappear from population in 24-48 hours if exposure large enough
What is the initial treatment of an acute radiation exposure?
1. Triage patient - ABC
2. Treat any wounds/trauma/burns/ decontamination
3. Secure patient
4. Monitoring - esp BP/HR/Temp
5. Treat vomiting (ondansetron/granisetron)
6. Bloods/FBC
- serioal lymphocyte counds imporant (Andrews lymphocyte nomorgram)
- repeat every 3-6 hours
7. Maintain oral feeding if possible (preferable to eneteral)
8. Antiviral/antifungal/antivbacterial coverage
9. GCSF improves time to recovery and should e administered within 24-72 hours
10. Meticulous hygience and environmental isolation
- GI decontamination
- ? sucralfate to avoid stress ulcers
ALSO consider
- KI to block radioactive Iodine uptake (if at risk)
- Radiogardase which bind Cs-137 in intestine and is expelled faecally
CONTROVERSIAL
- BMT may be useful inj range of 8-10Gy (<8 supportive care best, >10Gy unlikely to survive)
How does a lymphocyte count help after a TBI exposure?
lymphocytes are extremly sensitive to RT.
Serial FBE's and lymphocute depletion can estimate dose (? Andrews nomorgam)
2-4Gy: decline at 4-6 days
4-6Gy: decline in 2-4 days
Higher doses may cause decline within 24 hours
How long is a radiation response seen in blood cells lines?
lymphocytes: dose dependent
platelets - nadir 25-30 days
neutrophils - nadir 30-35 days
How do chromosome aberrations help to estimate dose following a TBI?
Asymmetric aberattions cn be counted (dicentrics and rings)
Doses as low as 0.25 Gray can be scored
Mature T cell lymphocutes have a life span of 1500 days and this test can be used for months to years follwoing exposure
What is the micronucleus assay?
cells are cultured in cytochalasin B which blocks cytokinesis and creates binucleate cells
Micronuclei are formed during exposure to RT and frequency increases with radiation dose
the number can be score to give a dose estimate
What is the comet assay?
Comet assay, also known as single cell gel electrophoresis measures DNA breaks
Cells are exposure to IR
Embedded in agarose
Lysed (neutral buffer for DNA DSB's, alkaline buffer for SSB's)
A volatage is applied across the sample
The migration distance is dependent on the size of the DNA which alters with the degree of DNA damage
What is the rationale for TBI?
Eradication of the recipient bone marrow
Immunosuppression to prevent rejection of donor marrow
Relative stromal sparing
What is the abscopal effect?
The abscopal, or bystander effect is the effect that radiation induced damage (i.e. cell kill/mutagenesis) may occur in cells that are not traversed by a particle of ionising radiation, but may occur by its close proxiimity to a cell that has
What are the subacute radiation syndromes?
1. Radiation pneumonitis
2. Somnolence syndrome
3. L'Hermittes syndrome
What is the underlying pathogenesis of L'hermittes sydnrome?
Transient demyelination
What is the tolerance of the lens?
Radiation causes posterior capsular cataracts (not nuclear).
Tolerance clearly increases with number of fractions and increasing overall treatment time.
single fraction 2.0Gy
Over 3-4/52 - 4.0Gy
Over 3 months - 5.5Gy
Latent period decreases with increasing dose (~8 years from 2.5-6.5Gy)
With high LET the RBE may be 50x.
What doses cause sterility in males
0.15Gy - oligospermia
>0.5Gy - temporary sterility
2Gy - can take up to 2-3 years to recover
Single 6Gy - permancnet sterility
6-8Gy in 2Gy fractions
What does causes male hormonal ablation?
? >20-30Gy
What does is required to cause sterilisation in females? What does to cause hormonal ablation?
Prepubertal - 12Gy
Premenopausal - 2Gy
Pronounced hormone changes occur with sterility
What is the dose to cause a second cancer?
Stochastic effect.
Working population: lifetime risk of mortality from malignancy estimated
Working population
0.08/Sv in high dose and 0.04/Sv in low dose/rate
General population
0.10/Sv in high dose and
0.04/Sv in low dose/rate
NB the risk of malignancy in utero is approximately 40% excess risk with pelvimetry and approximately 6% from Japanese data
What is the tolerance of the brain?
Endpoint: Necrosis
Quantec: 72Gy partial.
Emami: 60,55,45 Gy

Single fraction: 12Gy to less than 5-10cc
What is the tolerance of the brainstem?
Endpoint: necrosis (death)
Quantec:54Gy total brainstem (up to 59Gy for partial)
Emami: 60,53,50

SRS 12.5Gy < less than 5%
What is the tolerance of the brachial plexus?
Endpoint: plexopathy
Quantec: No data
Emami: 62,61,60
What is the tolerance of the spinal cord?
Endpoint: myelitis/opathy
Quantec: Max 50Gy (0.2% risk, 60Gy 6% risk, 69Gy 50% risk)
Emami:47Gy (20cm), 50Gy (10 and 5 cm)

SRS: 13Gy/1#, 20Gy/3# (<1% risk)
What are the lens and retina constraints from Emami?
10 and 45Gy
What is the tolerance of the optic chiasm and nerve?
Endpoint: blindness/partial blindness/RION
Quantec: Max 55Gy (rare below, 3-7% between 55-60Gy, increases rapidly)
Emami: 50Gy (appears inaccurate - no risk)
SRS - 10Gy (0 <8Gy, rises 8-12Gy)
What is the tolerance of the ear?
Endpoint:
Quantec: sensioneural deafness - </= 45Gy, <35 if concurrent cisplatin
Emami: acute otitis 35Gy, chronic 55Gy
SRS:14Gy
What are the dose constraints recommended for the larynx?
Endpoint: necrosis
Quantec:
Mean uninvolved dose 40-45Gy
Involved 63-66Gy
What are the traditional constraints (Emami) for parotid?
32Gy for xerostomia
What are the Quantec recommendations for parotid?
Endpoint: xerostomia
Mean dose: Limit one gland to < 20Gy or both to < 25Gy. submandibular sparing may reduce xerostomia (limit < 35Gy)
What are the Emami limits for larynx and pharynx to prevent dysphagia?
Dose to constrictors and larynx to be limited to not exceed 60 Gy where possible, and 50Gy if possible
Dose tolerances for small intestine?
Endpoint: stricture/fistula
Quantec:V15Gy <120cc Emami:45Gy
SRS : 12.5 Gy <30cc
What are the Quantec recommendations for the rectum (in prostate cancer)
V75 < 15
V70 < 20
V65 < 25
V60 < 35
V50 < 50
What are the Quantec recommendations for the liver?
Whole liver
Mets: ≤30Gy
Primary: ≤28Gy
Partial Liver
Mets <32Gy
Primary <28Gy

SRS:
Whole liver: 21Gy/7#
Liver-GTV
<13Gy/3#
<18Gy/6#
What are the quantec recommendations for the kidney?
Bilateral Kidney RT:
TBI < 10Gy
Non TBI < 18Gy

Partial
Bilat MKD: < 18Gy
V28<20
V23<30
V30<32
If dose to one kidney is >18Gy, then the other kidney should be V6<30
What are the quantec recommendations for the penile bulb?
95% of bulb <50Gy
V70 < 70
V50 < 90
What are the current recommendations for lung constraints?
Endpoint: for a RP risk of <20% in patients treated definitively for NSCLC
V20<30-35
MLD < 20-23
SRS: ?
What was Emami's dose constraints for femoral heads?
52Gy for Osteoradionecrosis
What are the Quantec recommendations for the heart?
MHD <15Gy
V25<10%
What are the Quantec recommendations for stomach tolerances?
V7/5 45Gy
V22.5 < 4% or 5cc
What is consequential late effect?
A consequential late effect is a late effect as a result of a severe acute effect.
What is a stochastic effect?
A stochastic effect is one which has no threshold, but the probabilty increases with dose, and the severity is not affected by the dose. i.e. carcinogenesis
overthrow
stürzen;
aus dem Weg räumen
What are the mechanisms of carcinogenesis following RT?
High dose - chronic injury and inflammation
Low dose - traditional causes i.e. incomplete repair of genetic damage
What is the risk of carcinogenesis arising from in utero exposure
Estimated increased rate of 40% following pelvimetry in 3rd trimester.
Excess risk is about 6%/Gy
Radiation doses around 10mGy seem to increase risk
Is low dose radiation beneficial?
Controversial. One needs to pick and choose data to come from conclusion. UK data showed increased rates of cancer mortality, but over diecrease in non cancer mortality, and compared to other physicians this had shown a decreased mortality ratio. The US showed increased overall and cancer related mortality.
What is the data from RT patients regarding secondary carcinogenesis?
Prostate patients have shown increased solid organ tumours in high dose region, but also in low dose region i.e. stomach and lung
Cervix patients have shown increased risk of bladder, vagina and rectum in high dose field. Low dose of several Gray increased risk of stomach cancer and leukaemia.
Amoong long term HL suvivors - the breast is parituclar sensitive to carcinogenesis, particular women <30
What is the in utero data from the Japanese atomic survivors?
1. Microcephaly
- no threshold
- most important at 0-7, and 8-15 weeks

2. Mental retardation
- may be a threshold of ~0.12-0.20 Gy
- Greatest risk 8-15 weeks, 4x less at 16-25 weeks
- risk is about 40% at 1 Gy, and is estimated to be 30IQ points lost/Gy
What is the medical exposure radiation data suggest for in utero exposure?
2-3 weeks: few abnormalities, all or nothing
4-11 weeks: severe abnormalities of organs
11-16 weeks: eye, skeletal and genital malformations, general growth retardation and mental retardation
16-25 weeks: microcephaly, stunted growth, mental retardation
30 + weeks: functioan abnormalities, and carcinogenesis
What is the doubling dose?
It is the dose of radiation requried to double the spontaneous mutation rate
Define sublethal damage.
Sublethal damage is the increase in cell survival when a dose of radiation is split in two and separated in time.
Define potential lethal damage.
Potential lethal damage is damage which would normally result in cell death, but which may be augmented due to changes in post irradiation environmental conditions (i.e. suboptimal growth conditions)
Define the volume effect.
The volume effect is the dependence of radiation damage to normal tissue to the volume of tissue irradiated.
Describe the volume effect in series arranged organs.
FSU's arranged in series show a volume effect because teh curve relating probability of a complication to dose rises much more steeply with dose and moves to lower doses. See fig 19.1 Hall
What is a blob?
a concentration of 12 ions pairs in a 7nm region (see spurs)
What is a chromatid?
Each of the two pogeny strands of a duplicated chromosome joined at the centromere during mitosis and meiosis
What is chromatin
the complex of DNA, RNA, histones, and nonhistone proteins that make up chromosomes
What is a chromosomal polymorphism
alternate structure or arrangents of a chromsome that are carried by members of a population.
What is a chromosome?
In eukaryotes it is a DNA molecule complexed wiht RNA and proteins to from a threadlike stucture containing genetic information arranged in a linear sequence.
What is a codon?
A group of three nucleotides that specifies the addition of one of the 20 amino acids during translation of mRNA into a protein
What is a concomitant boost?
a method of treatment acceleration via the addition of extra doses (received BD) to a smaller field in the later days of treatment to reduce overall treatment time.
What is a clonogen?
A clonogen is a cell which has the potential to form an expanding number of descendents.
What is DNA?
Deoxyribonucleic acid is an organic acid composed of four nitrogenous bases linked via sugar and phosphate units. It is the genetic material of most organisms and usually exists as a double stranded molecule in which two antiparallel strands are held together by hyrdogen bonds.
What is DNA polymorphism?
One or more alternate forms of a choromosomal locus that differ in nucleotide sequence or have variable numbers of repeated nucleotide units
What is dominance?
The expression of a trait in the heterozygous condition.
What is the dominant gene?
a gene whose phenotype is expressed if it present in a single copy.
what is double trouble?
the situation in which a hot spot within a treatment field receives not only a higher dose but also a higher dose per fraction, which means that the biological effectiveness of the dose is also much higher.
What is doubling time?
Doubling time is teh time it takes for a cell population or tumour volume to double its size
What is a free radical?
A free radical is a fragment of an atom or molecule that contains an unpaired electron which therefore makes it very reactive
what is a gene?
the fundamental physical unit of heredity whose existence can be confirmed vy allelic variants and that occupies a specific chromocomal locus OR a DNA sequence coding for a single polypeptide
What is gene amplification?
The presence of multiple copies of a gene oand one of the mechansims by which protooncogenes are activated to result in neoplasia
What is gene expression
the process of producing a protein from its DNA and mRNA coding sequences
What is heterochromatin
heavily staining late replicating regions of the chromsomes that are condensed in interphase.
What is the labelling index?
the percentage of cells in the opulation (S phase) i.e. the proportion synthesizing DNA
What is a karyotype?
arrangement of chromosomes from a aprticualr cell according to a well established system such taht the largest chromosomes are first and the smallest ones are last
What is latency period?
the time between an injury occurring and the effects of the injury expressing themselves as disease?
Define open reading frame
A long DNA sequence uniterrupted by a stop codon, that encodes part or all of a protein
what is penetrance
the frequency with which individuals of a given genotype manifest at to least come degree of a specific mutant phenotype associated with a trait
what is pleiotropy
condition in which a single mutation simultaneously affects several characters
What is ploidy?
Relates to the number of sets fo chromosomes in a cell. i.e. diploid 2, tetraploid 4.
what is a polymorphism
the presence of two or more discontinuous, segregating phenotypes in a population
what is a promoter?
a region of DNA extending 150-300 bases upstream from teh transcription start site that contains binding sites for RNA polymerase and a n umber of proteins that regulate the rate of trnasciption of the adjacent gene
what is a radionuclide?
a radioactive nuclide
what is a wild type mutation?
the most commonly observed phenotype or genotype, designated as the norm or standard
What is a translocation?
the movemnt or reciprocal exhange of large chromsomal segments typically between two different chromosomes
What is the therapeutic index?
therapeutic index is the tumour resonse for a fixed level of normal tissue damage
what is a spur?
a concentration of about 3 ion pairs in a volume of 4mm
what is a locally multiply damage site?
a wide variety of complex lesions, including base damage, single and double stranded breaks produced by spurs and blobs from high LET