Photocarcinogenesis Flashcards
(26 cards)
Define cancer
An accumalation of abnormal cells that muiltiply through cell division and spread to other parts of the body by invasion and/or distant metastases via the blood and lymphatic system.
Describe the disease process of cancer.
Cancers originate from a single cell. This cell will have mutated to give it a selective (growth) advantage. A series of mutations accumulate in successive generations in a process called clonal evolution. Eventually a cell accumulates enough mutations to become cancerous.
Hallmarks of cancer
Resisting cell death Sustaining proliferative signalling Inducing angiogenesis Evade growth suppressors Activate invasion and metastasis Enable replicative immortality.
Upcoming hallmarks of cancer
Deregulating cellular energetics- must be able to regenerate metabolism e.g. upregulate glycolysis
Avoid immune destruction- by hiding or changing the immune response
Genome instability- promote tumorogenesis (the production of tumours). Enhances its growthability e.g. draws cells that can produce growth factors
Oncogene
Increase cell division- mutated form of the protooncogene.
Tumour supressor
Suppress tumour growth
Risk factors for skin cancer
UV radiation, old age, muiltiple benign naevi, genetics, chemical exposure
Chronic long term UV radiation indicates which sorts of cancer
Squamous cell carcinoma
Intense intermittent and recreational UV exposure
Melanoma
BCC
Burning UV exposure
Melanoma
BCC
Artificial UV exposure
SCC
BCC
Melanoma
How is genetics related to skin cancer risk
Skin complexion inherited- types can be from 1-6
Also genetic pre-dispositions such as:
Albinism- Reduced or complete lack of pigment in the skin
Xeroderma Pigmentosum- XP associated genes associated with DNA repair.
How is immune suppression related to increased risk of cancer.
In transplant patients- immunosuppression is needed for the organs to be accepted. Means the immune system isn’t as equipped to deal with cancerous cell growth.
Autoimmune conditions
UC- 23% likelier to get malignant melanomas
Crohns disease- 80% likelier to get malignant melanomas
What does UVA do?
Causes indirect oxidative damage to DNA, however penetrates more deeply into the skin than UVB.
What does UVB do?
Directly causes DNA damage.
What types of UVB induced DNA lesions are there?
Cyclobutane pyrimidine dimers (CPD’s)
Pyrimidine-pyrimidine (6-4) photo producers
Both are formed by covalent bonding between adjacent pyrimidines on DNA strands.
How are UVB induced lesions repaired?
CPD’s and 6,-4 PP’s are relatively stable structures and are removed by nucleotide excision repair.
Nucleotide Excision repair
Recognition of damaged DNA
Cleavage of the damaged DNA on either side of the photo product
DNA polymerase fills in the gap, using the undamaged DNA strand as a template
DNA ligase seals it up.
Error prone DNA repair
Unrepaired UV induced photoproducts interfere with base pairing during DNA replication, leading to mutations.
In most cases, polymerase inserts the correct bases. However if polymerase is error prone it may not correctly give the structure of the lesion and insert the wrong base pair.
Indirect UV damage to DNA
UVA causes indirect DNA damage via oxidation of DNA bases especially deoxyguanosine to form 8-oxo deoxyguanosine.
8-oxo dG can mispair with deoxyguanosine rather than forming a normal base pair with deoxycytosine,
How are oxidised bases repaired?
Base excision repair
Describe base excision repair
Recognition of chemically altered base causing slight helix distortion.
Cleavage of the altered base from the deoxyribose by DNA glycosylase
Base free deoxyribose cleaved away by endonclease
Single nucleotide gap filled by DNA polymerase B
DNA ligase seals the end
UV induced immunosupression
Depletion of langerhans cells in the skin and reduced ability to present antigens
Generation of UV induced regulatory T cells with immune supressive activity
Secretion of anti-inflammatory cytokines.
Basal cell carcinoma mutations
Mutations in the PTCH1 are associated with BCC
