DNA damage Flashcards
what is cancer
Adaptive development of of misgrowth of normal human cells
Cancer can form tumours - distant metastasis cause problems when they are not contained
T/F blood cancers can also form tumours
False
how are cancer cells different from normal cells
- Grow in the absence of signals telling them to grow and ignore the signal which tell them to stop dividing/to die
- hide from the immune system/subvert immune system into helping cancer cells stay alive
- accumulate multiple changes in their chromosomes.
- Rely on different kinds of nutrients / make energy from nutrients in a different way than most normal cells
how does cancer move around the body
Accumulates in tumours (growths) and recruits blood vessels to grow around
- burst of tumours cause metastasises and spread of cancers
why is cancer considered a heterogenous disease
- every tumour is unique, and even a single tumour will contain different populations of cells
why is cancer difficult to treat
- heterogenous disease
- ever changing cells develop survival methods faster than they are killed
- Drug treatment leads to the evolution and selection of drug resistant tumour cells – the disease becomes refractory to treatment
- Current drug discovery strategies aim to target the identified differences between normal and tumour cells – individual profiling of disease
- However, most currently-used drugs are not exclusively active against tumour cells. Thus treatment causes unpleasant and sometimes dangerous side effects
Cancer incidences increase with _. Why?
Age
- two hit hypothesis
what is the two hit hypothesis
- Loss of tumour suppressor function requires both alleles to lose function – two-hits that take time or large amounts of damage to occur in normal cells
- The older you are, the more likely to lose allele function
- Germline mutation such as BRCA (breast cancer) were one allele is dysfunctional from birth and therefore the risk of developing two dysfunction allele
= First hit has bigger impact
Why is cancer considered a ‘Disease of the Genome’
- Cancer is a family of diseases that can arise in many different tissue types
- Cancers share the common property of uncontrolled growth of tumour cells
- Cancer is caused by the accumulation of mutations in the genome arising from DNA damage
what genes are normally mutated in cancer
Oncogenes (positive regulators of cell growth)
Tumour suppressor genes (negative regulators of cell growth)
Apoptosis and lifespan-regulating genes (cell death pathways)
Mutator (caretaker) genes (DNA damage surveillance and repair)
what envirometal factors can cause cancer
Sex, Alchol, stress, immunosuppresion, Viruses, bacteria, parasites.
X-irridiation UV irridation, Anti cancer drugs, Aflatoxin/nitrosamines, Benzopyrenes
How does cigarette smoke cause cancer
Benzo[a]pyrene (BP) is metabolised in the body to BPDE (benzo[a]pyrenediol-epoxide) which forms a covalent adduct with guanine in the DNA
how has plant fungi been linked to cancer
Aflatoxin is metabolised in the liver to the oxidised form which binds covalently to guanine in the DNA
how does ionising radiation link to cancer
○ X rays cause oxidative damage to DNA
- Hydroxyl Radicals (OH.) damage nucleic acids.
- They are produced as a result of the hydrolysis of water by ionizing radiation
What is UV radiation
○ UVA = produces mainly reactive oxygen species (ROS)
(Responsible for majority of sunburns and can cause skin cancer, 320-400 nm = 95% of UV reaching the earths surface)
○ UVB = produces thymine photoproducts in the DNA
(penetrates deeper into the skin, causing ageing but contributes much less towards sunburn, 280-320 nm = Most of the UVB is absorbed by the ozone layer)
○ UVC = (most dangerous of all, but is completely blocked by the ozone layer, 290 nm = UVC is absorbed by molecular oxygen)
