17 - Cutaneous Photobiology Flashcards
Radiation can only cause a photobiologic response if
It is first absorbed by a molecule (chromophore) in the skin
UV-signature mutations
C to T and CC to TT mutations at dipyrimidine sites
Y/N: Photoaging is reversible.
No
Carries sufficient photon-energy to completely remove an electron from an atom or molecule
Ionizing electromagnetic radiation
Examples of ionizing electromagnetic radiation
X-rays
Gamma rays
Shortest wavelength of solar electromagnetic radiation reaching the earth’s surface
290 nm
Y/N: Longer wavelengths of UVR are highly damaging to animals and plants
No - shorter wavelengths
Energy (increases/decreased) with increasing wavelength
Decreases
ROYGBIV is arranged according to increasing
Wavelength
Spectrum of electromagnetic radiation from lowest to highest energy
Radio waves Infrared Visible Ultraviolet X-rays Gamma rays
Roman men Invented Very Unusual Xray Guns
(Shorter/longer) wavelengths of visible light are more filtered by a linger passage through the atmosphere
Shorter
Fraction of UVA relative to UVB (increases/decreases) with lower angles of solar radiation
Increases
Y/N: UVA and UVB are less abundant early or late in the day
Yes
States that light must be first absorbed by a chemical substance for a photochemical reaction to take place
Grotthuss-Draper law
One wavelength that is most likely to excite a chromophore
Absorption maximum
Well characterized chromophores in the skin (3)
DNA
Porphyrins
Melanin
Process in which energy from an excited chromophore is transferred to another molecule
Photosensitized reaction
States that the wavelength of fluorescence is always longer (=less energetic) than the exciting wavelength
Stokes law
Photon emission from return of triplet excited states to ground states
Phosphorescence
Major role of vitamin D
Increase the flow of calcium into the bloodstream
Safe upper limit for adult intake of vitamin D
10,000 IU/day
Chronic toxic dose of vitamin D
50,000 IU/day
When obtained from food or supplements, vitamin D is absorbed in the
Small intestine
Central role in photoaging
UVA
Immediate erythema and pigment darkening
UVA
Major role in drug induced photosensitivity
UVA
Major role in carcinogenesis
UVB
Role in vitamin D production
UVB
25(OH)D-1alpha-hydroxylase activity is increased by (2)
Parathyroid hormone
Low phosphate
In tropical areas, adequate amounts if vitamin D3 can be made in the skin with
10 to 15 minutes of biweekly sun exposure to the face, arms and hands, or the back
Most of the immunosuppressive effects of UVR are caused by
UVB
Chromophore for the sunburning and tanning reaction
DNA
Plant-based chromophores related to psoralens
Furocoumarins
Chromophore is the perfume ingredient bergamot oil (5-methoxy psoralen)
Berloque dermatitis
Most common indication for phototherapy
Psoriasis
Chromophore that mediates the antipsoriasis therapeutic efficacy
DNA
Much less energetic and produces much less pyrimidine dimers (UVA/UVB)
UVA
Chromophore that mediates the therapeutic effect of PDT
Protoporphyrin IX
Can penetrate through window glass
UVA
Almost monochromatic emissions at 311-312 nm
Phillips TL01 fluorescent lamp
Protoporphyrin is most effectively excited by (blue/red light)
Blue light
Deeper penetration of PDT with (blue/red light)
Red light
PDT modality more effective for thicker skin lesions, for example, infiltrating skin cancers
Methyl aminolevulinic acid (MAL) with red light
Y/N: Photoabsorbing molecules are usually larger and aromatic and are therefore less likely to be internalized by cells
Yes
Except chromophore of current PDT
Two main types of DNA photoproducts
Cyclobutane pyrimidine dimers
6,4-pyrimidine-pyrimidone photoproducts
Absorption maximum of DNA
260 nm
SCC and AK genetic mutations
p53
BCC genetic mutations
Sonic hedgehog signaling pathways (ptch, shh, smo)
p53
Melanoma genetic mutations
CDKN2A
PTEN
TERT promoter
p53
Mechanisms by which UVR induces formation of pyrimidine dimers (2)
Direct absorption of photons by DNA bases
Photoexcitation of melanin, particulary pheomelanin leading to formation of “dark cyclobutane pyridimine dimers”
Non-exposed cells in the vicinity of irradiated cells
also demonstrate stress responses similar to exposed
cells
Bystander effect
Most of the oxidative DNA damage after exposure to natural sunlight is caused by
UVA
Much higher abundance in natural sun (UVA/UVB)
UVA
Generating the majority of solar radiation-induced pyrimidine dimers (UVA/UVB)
UVB
Does not induce a robust cellular DNA damage response (UVA/UVB)
UVA
Melanomas that are not UVR-induced
Mucosal
Acral
Melanomas on chronically sun-damaged skin often arise from
Lentigo maligna
Non-chronically sun-damaged skin melanomas are most common on the _____ in wowen and on the _____ in men
Lower legs
Back
Damaged nucleotide is removed and
replaced with undamaged DNA
Nucleotide excision repair
Defects in nucleotide excision repair genes can cause
Xeroderma pigmentosum
Cockayne syndrome Trichothiodystrophy
Simpler type of DNA damage involving chemical changes in a single DNA base
Oxidative base modifications
DNA repair pathway for oxidative base modifications
Base excision repair
Guardian of the genome
Tumor suppressor p53
Group of cysteine proteases that are central regulators of apoptosis
Caspases
Only nonproliferative feature of photoaged skin that is not observed in intrinsically aged skin
Actinic elastosis
Accumulation of fibrillary basophilic material in the upper and middermis
Actinic elastosis
Progerin is found in high concentrations in cells from patients with
Hutchinson Gilford progeria
Advantage of MAL vs 5-ALA
Better uptake into cells because of is more lipophilic properties