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29 Cards in this Set

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