Cancer And DNA Flashcards
Name a few characteristics of cancer cells
Grow in the absence of growth signals
Ignore apoptosis signals
Spread to other areas of the body
Accumulate changes in their chromosomes
Why is cancer so difficult to cure
Every tumour is unique - single tumour contains diff populations of cells
Treatment leads to evolution of drug resistant tumour cells
What are the current aims and strategies of cancer drug discover
Identify underlying molecular pathologies
Target the identified differences between normal and tumour cells
Describe Knudson’s Two Hit hypothesis
In order for a cell to become cancerous both of the cells tumour suppressor genes must be mutated
Describe cancer
Family of genetic disease caused by germline and somatic mutations and chromosomal aberrations
What causes cancer
The accumulation of mutations in genome arsing from DNA damage
What genes are mutated in cancer
Oncogenes (+tive regulators of cell growth)
Tumour suppressor genes (-tive regulators of cell growth)
Apologise and lifespan-regulating genes
Mutator genes (DNA damage surveillance and repair)
Name a few environmental factors that can lead to cancer
Sex -> HPV -> Cervical
Alcohol -> Cirrhosis -> Liver
Stress -> Inflammation -> Various
Viruses -> EBV -> Burkitt’s lymphoma
Name examples of environmental carcinogens
X -irradiation -> radiotherapy -> breast
UV irradiation -> sun -> skin
Anti cancer drugs -> chemotherapy -> leukaemia
Benzopyrenes -> tobacco -> lung
What influences ‘the cancer lottery’
Casual mechanism in loving evolutionary mismatches and intrinsic fallibility
= mutations that enable increased cell survival
-> Darwinian selection will then select for these ‘positive attributes’
Describe the mechanism of DNA damage by carcinogens
Metabolised in body -> electrophiles that react w nucleic acid
E.g benzo[a]pyrene -> BPDE -> covalent adduct + guanine
Describe the mechanism of DNA damage by ionising radiation
X-rays cause oxidative damage to DNA
OH radicals damage nucleic acids
Result of hydrolysis of water by ionising radiation
Describe the mechanism of DNA damage by UV radiation
UVA: produces mainly reactive O2 species (ROS)
UVB: produces thymine photoproducts in the DNA
Describe the absorptions of the 3 types of UV
UVA 320-400nm - 95% reaching earth surface
UVB 280-320nm - Most absorbed by ozone layer
UVC <290nm - absorbed by O2
Describe the mechanism of DNA damage by sun damage
UV damages some cells -> can’t be repaired and are destroyed as risk of becoming cancerous
Some damage may remain, increasing cancer risk
What are the 3 types of UV
UVA: penetrates deep into skin, causes ageing
UVB: responsible for sunburns and can cause cancer
UVC: most dangerous of all, blocked by ozone
Describe the mechanism of DNA damage by chronic infections
Chronic infections lead to persistent inflammation at sites of infection = damage to cells
Describe the mechanism of DNA damage by endogenous causes
Hydrolysis of glycosyl bonds = base loss in DNA
Exposure to free radicals and oxidation
Methylation of bases in DNA via SAM
Replicating errors by DNA polymerase = deletions
Spontaneous decay of DNA
What is one of the most server side effects of cancer therapies
Diagnosis of second primary cancers unrelated to original ancerts
Describe the mechanism of DNA damage by DNA replication
Template lacks necessary information to form correct sentence =
Insertion of wrong base
Addition/deletion of short sequences
Double strand breaks
What are the consequences of incorrect DNA replication
Loss of chromosome segments
Exchange of sequence (recombination)
Stalling of replication fork @ damaged sites
What are the 2 most frequently mutated genes in smoking related lung cancer
K-ras (oncogenes) and p53 (tumour suppressor)
Benzo[a]pyrene linked to these mutations
How does benzo[a]pyrene cause a mutation
It’s epoxide binds to guanine in nucleus
If unrepaired G-C -> T-A (trans version mutation)
How does the K-ras oncogene
