W25 UV Radiations and skin cancer Flashcards
UV Radiation reaching the Earth contains how much UVA and UVB?
Which UV penetrates deeper?
▪ 95% UVA
▪ 5% UVB
- UVA penetrates deeper
▪ Reaching the dermis (20% deep dermis) - UVB have lower penetration
▪ 70% the stratum corneum,
▪ 20% lower epidermis sublayers,
▪ 10% the dermis
What are the 3 types of UV radiation?
- UVA - Longest wavelength (320-400nm)
▪ Can pass through the ozone and clouds (even glass) - UVB - Intermediate wavelength (320-400nm)
▪ Filtered by the Ozone layer and clouds - UVC - Shortest wavelength (100-290 nm)
▪ Do not reach the Earth (absorbed by the ozone)
What does UVA cause?
higher penetration
▪ skin ageing, wrinkles
▪ Potential DNA damage → cancer risk
What does UVB cause?
lower penetration
▪ Tanning: Melanocytes stimulation to release melanin → skin pigmentation
▪ Redness: Vasoactive mediator → inflammatory responses
▪ Sunburn: At high dose, inducing keratinocyte apoptosis
▪ Vitamin D3 biosynthesis
▪ Skin cancerogenic (more than UVA) → Risk of skin cancer development
Vitamin D3 biosynthesis:
What are the 3 affecting factors that reduce the process?
- UVB photons are absorbed by 7-dehydrocholestrol (PRO-Vitamin D3) in the epidermis, which is photochemically converted into PRE-vitamin D3
o Ageing
o sunscreen
o melanin levels/skin pigmentation
- Pre-vitamin D3 undergoes a thermal isomerisation to form vitamin D3 (within 24/48h)
- Endogenous or dietary Vitamin D3 is released into the bloodstream
- Vitamin D3 can also be obtained with the diet (limited) and supplementation
Vitamin D3 synthesis
What is vitamin d3 converted into in the liver and kidneys?
- Vitamin D3 (inactive) is converted to 1,25-
dihydroxyvitamin D3 (calcitriol – active
form) by two hydroxylations in the liver and
kidneys - Calcitriol acts as a hormone:
➢ Ca++ & phosphate homeostasis in target organs
- Calcitriol acts as a hormone:
Vitamin D3 effect in the skin
What is thr role of keratinocytes?
- Keratinocytes respond to vit. D3 or analogues → psoriasis treatments
▪ They include the nuclear vitamin D receptors (VDRs)
▪ Vitamin D3 deficiency is associated with psoriasis and atopic dermatitis - Vit. D3/receptor complex acts as transcription factors
- Interacts with DNA regions to modify gene expression regulating:
▪ Reducing the proliferation rate of stem cells in S. basale
▪ Regulating keratinocytes differentiation –keratin granules and lipid
production – to maintain the skin barrier integrity
▪ Mild immunosuppression to obtain an anti-inflammatory effect
Phototherapy
What is it used to treat?
What are the 2 main forms?
- Skin treatment → controlled administration of UV radiation
➢ Psoriasis
➢ Chronic Eczema
➢ May be beneficial for acne, Vit. D3 deficiency, vitiligo - Narrowband UVB
- PUVA – Psoralen with UVA
-Typically, 2–3 times per week for 6–10 weeks until skin lesions are cleared
Typically, 2–3 times per week for 6–10 weeks until skin lesions are cleared
Narrowband UVB wavelength - (311-312 nm)
- Same effects of UVB but better tolerated and less cancerogenic
- Can be combined with topical retinoids, vit. D3 analogues, & steroids in difficult cases
PUVA → in patients who have failed to respond to UVB
* Combining Psoralen (natural phototoxic molecule) & UVA
What is the mechanism?
▪ Psoralen is taken (topically or orally) 2 hrs before UVA exposure
▪ UVA photons activate psoralen → becoming phototoxic to:
➢ interferes with DNA → reducing mitosis and keratinocytes formation
➢ Induces apoptosis in Langerhans cells → immunomodulation and anti-inflammation
Phototherapy mechanism in psoriasis
What are the 4 effects?
- Anti-inflammation effect:
Dec cytokine production
Dec keratinocyte proliferation - Keratinocytes regulation
Dec mitotic activity
Inc keratinocytes apoptosis
Activating procaspase 3 into caspase 3=
Apoptotic pathway and DNA degradation - Antipruritic effect
- Immunosuppression effect
Dec infiltration of T cells
Dec Langerhans cells activation/apoptosis
What are the Short term adverse effects of phototherapy? (5)
- Skin rash, blistering
- Nausea (only PUVA)
- Increased insensible water loss
- Bronze baby syndrome → harmless greyish-browndiscoloration of the skin
- May result in hypocalcaemia
What are the Potential long-term adverse effects of phototherapy?
- Skin ageing
- skin cancers → cancerogenic (higher risk with PUVA)
▪ PUVA is not suitable for long-term use
What is skin cancer?
- Potentially serious condition
- Three main types of cancer affecting:
▪ various cells
▪ distinct stratums of the epidermidis - Largely preventable
- Uncontrolled cell divisions of cancerous cells,
lose of cell differentiation/specialisation/shape
oncogenes and tumour suppressor genes are mutated
UV radiation contribute to DNA damage:
- Free radicals generation → DNA degradation
- UVB induce incorrect base pairing between
non-complementary bases of a duplex DNA e.g thymine and thymine
▪ Cells can repair DNA mutations, but not always
▪ Unrepaired mutations can distort DNA → breaks
▪ Altering expression or products of key genes
