Flashcards in DD Ultraviolet Damage and Repair Deck (20):
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
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
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
Negative effects of UVB
Cell cycle changes
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?
1. Leukocyte migration into the skin
UVR Induced Immunosuppression
- UVR decrease in Langerhans Cell populations
-UVR induction of inhibitory cytokine network:
IL10, TH2 cytokine pattern
-Tolerance induced by Suppressor cells
Is UVR immunosuppression inhibited by high melanin content?
it potentiates induction of NMSC (non-melanoma skin cancer)
is a family of diseases in which genetic defects in DNA repair lead to premature aging of the skin and fatal induction of UVR-induced skin cancers
Defenses against Reactive Oxygen in the Epidermis
-Peroxidases and catalases
Melanocytes are situated in which layer of the skin
1. UV Exposure
2. DNA Damage
3. Formation of Mutations
4. Multistage Carcinogenesis