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29 Cards in this Set
- Front
- Back
Spectrum of UVA (UVA1, UVA2)?
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UVA 400-320nm
UVA1 400-340nm UVA2 340-320nm 90% of radiation that hits the earth |
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Spectrum of UVB?
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320-290nm
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Spectrum of UVC?
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200-290nm
Almost completely absorbed by ozone |
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When does UVB erythema occur? UVA?
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UVA = immediate
UVB = 6-24 hours after exposure |
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Describe the Tanning response:
UVA vs UVB |
UVA tan = immediate pigment darkening, alteration (ex., oxidation) and redistribution of existing melanin.
UVB tan = delayed tan, peaks 3 days after exposure due to increased # of melanocytes, melanin synthesis, arborization of melanocytes and transfer of melanosomes to keratinocytes |
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UVA vs UVB and role in photoaging vs photocarcinogenesis
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UV'A' --> photo'A'ging (due to penetrance into dermis)
UVB --> photocarcinogenesis due to cells residing into epidermis |
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When does UVB induced sunburn occur? What is the chromophore?
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DNA = Chromophore for UVB, unknown chromophore for UVA.
UVB = Burns Burn peaks 6-24 hours after exposure (immediate erythema rarely observed, unlike with UVA) |
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Where do BCC, SCC & Lentigo Maligna arise from versus Melanomas?
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Chronically sun damaged skin -- BCC, SCC, Lentigo maligna
Intermittently exposed areas -- melanoma |
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Theory behind UV induced melanomas?
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UV induced mutagenesis after single high dose of UV, causes inability to undergo apoptosis --> elevated levels of anti-apoptotic proteins (Bcl-2)
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What is the Max Absorption wavelength of DNA?
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260nm
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In vivo, what is the wavelength most effective for inducing photoproducts?
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300nm (UVB)
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What are the two major pyrimidine dimers? Which is more common?
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Cyclobutane-pyramidine dimers *MC* (Thymine-Thymine dimers are MC of the CPDs)
6,4 Photoproducts |
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What is a 6-4 Photoproduct?
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Covalent link b/tw C-6 and C-4 of two adjacent pyramidines, aka "non-cyclobutane dipyramidine photoproduct". Thymine-Cytosine (T-C) is the most common.
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What gets up-regulated in the cellular damage pathway?
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p53: cell cycle arrest, DNA excision repair, apoptosis.
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Difference between Type I and II photosensitized reactions
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Type I: Energy from other chromophores transferred to DNA
Type II: Energy abs by molecular oxygen making reactive oxygen species which can damage DNA |
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Give examples of UV induced Reactive Oxygen Species and their products.
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Singlet Oxygen (guanine --> 7,8-dihydro-8-oxyguanine
Hydrogen Peroxide (combines with nuclear metals to form hydroxyl radicals) Superoxide Radical |
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What pathway repairs DNA? What condition results if this pathway is defective?
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Nucleotide excision repair (NER) - transcription coupled repair
Condition: Xeroderma pigmentosum (XPA through XPG) |
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Name d/o with NER defects
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XP
Cockayne Syndrome Trichothiodystrophy |
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What are characteristics of XP?
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1. Photosensitivity
2. Cancer-proneness 3. Neurologic deficits (in some) ** Note: phenotype does not correlate with DNA repair defect type ** |
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What are the most common variants of XP ?
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75% of cases are: XPA, C, and V (Variant)
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Most common XP in Japan?
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XPA -- shows neurologic deficits
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Most common XP in US?
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XPC - milder phenotype
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Which XPs are assoc with TTD and XP-Cockayne?
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XPB & XPD
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XP Variant has mutation in which gene?
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- Pol-n gene (defective post replication repair)
- DNA Polymerase-n, unable to correctly insert two A residues - causes UV-mutator phenotype |
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Describe Steps to Base Excision Repair
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Processes non-bulky oxidative DNA base modifications
Removes base (rather than nucleotide) by DNA glycosylase |
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What enzyme specifically targets oxidized guanine bases?
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8-oxoG DNA glycosylase 1 (hOGG-1)
Loss of this enzyme creates hypersensitivity to UVA |
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What UV induced mutations are involved in skin cancer development?
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1. Ras oncogene
2. p53 tumor suppressor (critical gene for induction of apoptosis -- seen in AKs and SCCs, accumulation of mutated p53 is needed; seen in late melanoma) 3. PTCH tumor suppressor (BCCs) 4. p16 tumor suppressor (melanoma) |
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Li-Fraumeni syndrome has which mutation?
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p53 tumor suppressor gene mutation
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Eumelanin vs Pheomelanin
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Eumelanin can help scavenge a superoxide radical; pheomelanin is NOT as effective -- acts more like a photosensitzer
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