DD Ultraviolet Damage and Repair Flashcards
UVR (UVB+UVA) damage to skin includes:
1) Damage to RNA, DNA, lipids, and proteins.
2) Pro-inflammatory effects
3) Immunosuppressive effects
4) Induction of innate defenses
5) Induction of apoptosis
6) Vitamin D synthesis
UVB radiation
Main cause of sunburn and tanning on skin, as well as Vit D3 formation.
UVB contributes to higher carcinogenesis than at larger wavelengths such as UVA.
Vitamin D synthesis via sunlight (UVR)
Cholecalciferol (VitD3) and ergocalciferol (VitD2) (also available through diet) –> converted to active form in liver and kidney (Di-hydroxy Vitamin D3)
UVA physiological changes
premature aging, loose skin, wrinkles, dark patches, and DNA damage
□ Used in tanning beds; most effective at inducing ROS and immunosuppression.
□ Penetrates deeper into dermis, thus act on fibroblasts and CT b/c of longer wavelength.
- low energy
UVB physiological changes
DNA damage, sunburn, and eye damage.
□ Act principally on keratinocytes, melanocytes, and Langerhans cells (DC of skin) b/c of shorter wavelengths
-high energy
UVC
Filtered out by ozone typically
Which, UVB or UVA is most associated with skin cancer?
UVB >UVA with non melanoma skin cancer,
UVB=UVA in melanoma
Particularly for UVR, main types of DNA damage are
§ Thymine dimer (UVB)
§ Pyrimidine-6-4-pyrimidone (UVB)
§ Hydroxyguanosine (UVA and singlet oxygen)
Negative effects of UVA
Oxidative damage
Base modification
Bbasic sites
Strand breaks
Negative effects of UVB
Cell cycle changes
Mutations
Cyclopuridine dimers
Photoproducts
Melanocytes
Functional “slaves” to keratinocytes that produce melanosomes that contain melanin.
• Increased melanogenesis occurs in response to UVR. Keratinocytes detect UVR, signal melanocytes to increase melanin production.
Outcome of DNA Damage
- Repair of Damage
- Induction of Apoptosis
- Gene Mutation
- Carcinogenesis initiation, transformation and progression
What does UVR induce?
- Leukocyte migration into the skin
- Inflammation
- Immunosuppression
UVR Induced Immunosuppression
- UVR decrease in Langerhans Cell populations
-UVR induction of inhibitory cytokine network:
IL10, TH2 cytokine pattern
-Tolerance induced by Suppressor cells
Treg (CD4+CD25+)
NKT cells
Is UVR immunosuppression inhibited by high melanin content?
no.
it potentiates induction of NMSC (non-melanoma skin cancer)