Cancer Bio (Dan Lecture 3 - DNA damage) Flashcards
Name come common types of DNA damage?
- Oxidation
- Methylation
- Strand breaks
- Bulky adducts
- Cross links
Name some DNA damaging agents
- UV
- Cigarette smoke
- Dyes
- Ionising radiation
- Chemotherapy
- Foods?
Name some types of endogenous DNA damage
- Deamination (e.g. cytosine to uracil)
- Oxidation
- Methylation
- Lipid peroxidation
Name some types of exogenous DNA damage
- Pollutants
- UV
- Ionising radiation
- Ciggy smoke
Name the repair processes responsible for the repair of the following:
1) Oxidative damage and SSBs
2) Bulky adducts, CPDs and 6-4PPS
3) Cross links and DSBs
4) Mismatches, insertions or deletions
1) Base-excision repair
2) Nucleotide excision repair
3) Recombinational repair
4) Mismatch repair
What are the potential consequences if DNA damage is not repaired?
1) Cell cycle arrest
2) Apoptosis
- caused by inhibition of transcription, replication or chromosome segregation
3) Cancer, Ageing
- Caused by mutations and chromosome abrrations
What are the 3 classifications of UV radiation and what is the wavelength of each?
UVA (320-400nm)
UVB (295-320nm)
UVC (100-295nm)
Why does solar radiation contain 95% UVA with the rest UVB?
Because the ozone absorbs UV with wavelength below 300nm
What year was UV classified as a human carcinogen and by which body?
Internation Agency for Research on Cancer 1992
What are the 3 types of skin cancer and what are the characteristics of each?
1) Basal cell carcinoma
- Relatively common
- Can be invasive
- Rarely metastatic
2) Squamous cell carcinoma
- Less common
- Significant risk of metastasis to lymph nodes
3) Melanoma - affecting melanocytes
- Rare
- Highly invasive
- Common metastasis
- 75% of skin cancer death attributed to melanoma
Describe the penetrance of different UV types
UVA is lower energy but has higher penetrance than UVB
What countries have the highest rates of skin cancer?
Australia and New Zealand
Why are skin cancer rates so high in Australia and NZ?
1) Thin layer of ozone
- allows more UV exposure
2) Culture
- Outdoor lifestyles
- Fashion of the tan
- Society of not applying sun cream
- Slip, slop, slap campaign in 1981 to try and introduce sun protection into Australian society
3) Skin tone
- Movement of fair skinned Europeans in 18th century
What are the main 2 types of cancer relevant DNA damage induced by UV?
1) Cyclobutane pyrimidine dimers (CPD)
2) (6-4) pyrimidine-pyrimidone photoproducts (6-4PPS)
What is the structure of CPDs and 6-4PPs?
CPDs:
- covalent link between adjacent pyrimidine bases
- due to saturation of 5,6 double bonds, predominantly in the cis-syn conformation
6-4PPs:
- linking the C6 of the 5’ pyrimidine with the C4 of the 3’ pyrimidine