UV Radiation and DNA repair Flashcards
__________ radiation is responsible for most of the effects of the sunlight on the body?
uv-b
___ radiation is the main cause of sunburn and tanning
uv-b
___ radiation is main cause of formation of VitD3
uv-b
UV-B penetration
not fa - most is absorbed in the superficial tissue layers of 0.1mm depth
UVR effects on skin (6)
damage to DNA/RNA/protein/lipid
pro-inflammatory effects
immunosuppressive effects
induction of innate defense
induction of apoptosis
vitD synthesis
Most skin cancers are caused by?
UVA and UVB UV rays
UVB biological consequences?
eye problems
sunburns
UVB penetration?
just epidermis
UVA biological consequences?
dartk patches
wrinkles
loose skin
premature aging
UVA penetration?
through dermis
Erythema action spectrum is highest at?
low wavelength UVB (290nm) - so most sunburn is UVB dependent
melanoma
UVA and UVB
DNA damage primarily
UVB
NMSC?
mainly UVB
Erythema?
mainly UVB
Immune suppression?
mainly UVA
UVB affected cells?
kertinocytes
melanocytes
langerhaans
UVA affected cells
In addition to those in epidermis (kertinocyte, melanocyte, langerhaans)
also those in dermis
- fibroblast
- vessle and CT damage
what is present in skin that is converted to vitD3
7-dehydrocholesterol
DNA damage indueced by UVR?
Thymine dimer?
Pyrimidine-6-4-pyrimidone?
Hydroxyguanosine (free radicals)?
UVB
UVB
UVA
mainly responsible for oxidative damage and base modifications?
UVA
mainly responsible for strand breaks / mutation / cell cycle changes
UVB
Outcome of DNA damage to skin (3)
repair
induction of apoptosis
gene mutation
–> carcinogenesis initiation, transformtion, progression
basal and apoptosis
more resistant
What contributes to the erythema and oedema you seen in sunburn?
leukocyte extravasation and migration to the inflammatory sunburn
cytokines are induced by UVR
UVR induces inflammation by?
mediated by primary and secondary cytokines as well as lipids - erythema and sunburn cells potentiate other types of cutaneous inflammation (adhesion molcules, induction, cytoine and chemokine release)
Important mediators released by UVR
Primary cytokines?
IL-1a / TNF-a
Important mediators released by UVR
Secondary cytokines?
IL-6, IL-8, IL-10, GM-CSF
How does DNA damage via UVR cause immune suppression
via preferentially stimulating TH2 –> cytokine IL10 TNFalpha –> suupress cell induction?
UVR and langerhaans
reduces langerhaans cell population
UVR and inhibitory cytokine
IL10 / TH2
Is UVR immunosuppression inhibited by high melanin content?
No - so it will not be affected by black vs white
What does UVR immunosuppression potentiate?
induction of NMSC
Skin defenses against UVR? (4)
DNA repair
Apoptosis
Defenses against ROS
Melanin
________________ is a family of diseases in which genetic defects lead to premature aging of the skin and fatal induction of UVR induced skin cancer
xeroderma pigmentosum
What activates DNA repair enzymes following exposure to UVR
p53 activation by UVR
Defenses against ROS in epidermis?
peroxidase and catalase
superoxide dysmutase
glutathione reductase
thioredoxin reductase
albinism
defective?
tyrosinase
tyrosinase
converts tyrosine to dopa which is beginning of melanin production cascade
Who knows to make more melanin?
surrounding keratinocytes are principle detectors of UVR adn they signal melanocytes to increase melanin production as well as melanocyte proliferation
SPF refers to?
UVB rating
