DD Ultraviolet Damage and Repair

Question 1

UVR (UVB+UVA) damage to skin includes:

Answer 1

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

Question 2

UVB radiation

Answer 2

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.

Question 3

Vitamin D synthesis via sunlight (UVR)

Answer 3

Cholecalciferol (VitD3) and ergocalciferol (VitD2) (also available through diet) –> converted to active form in liver and kidney (Di-hydroxy Vitamin D3)

Question 4

UVA physiological changes

Answer 4

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

Question 5

UVB physiological changes

Answer 5

DNA damage, sunburn, and eye damage.
□ Act principally on keratinocytes, melanocytes, and Langerhans cells (DC of skin) b/c of shorter wavelengths

-high energy

Question 6

UVC

Answer 6

Filtered out by ozone typically

Question 7

Which, UVB or UVA is most associated with skin cancer?

Answer 7

UVB >UVA with non melanoma skin cancer,

UVB=UVA in melanoma

Question 8

Particularly for UVR, main types of DNA damage are

Answer 8

§ Thymine dimer (UVB)
§ Pyrimidine-6-4-pyrimidone (UVB)
§ Hydroxyguanosine (UVA and singlet oxygen)

Question 9

Negative effects of UVA

Answer 9

Oxidative damage
Base modification
Bbasic sites
Strand breaks

Question 10

Negative effects of UVB

Answer 10

Cell cycle changes
Mutations
Cyclopuridine dimers
Photoproducts

Question 11

Melanocytes

Answer 11

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.

Question 12

Outcome of DNA Damage

Answer 12

• Repair of Damage
• Induction of Apoptosis
• Gene Mutation
• Carcinogenesis initiation, transformation and progression

Question 13

What does UVR induce?

Answer 13

1. Leukocyte migration into the skin
2. Inflammation
3. Immunosuppression

Question 14

UVR Induced Immunosuppression

Answer 14

• 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

Question 15

Is UVR immunosuppression inhibited by high melanin content?

Answer 15

no.

it potentiates induction of NMSC (non-melanoma skin cancer)

Question 16

Xeroderma Pigmentosum

Answer 16

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

Question 17

Defenses against Reactive Oxygen in the Epidermis

Answer 17

• Peroxidases and catalases
• Superoxide dysmutase
• Glutathione reductase
• Thioredoxin reductase

Question 18

Melanocytes are situated in which layer of the skin

Answer 18

Basal

Question 19

Photocarcinogenesis Cascade

Answer 19

1. UV Exposure
2. DNA Damage
3. Formation of Mutations
4. Multistage Carcinogenesis
   Initiation
   Promotion
   Transformation

Question 20

Sunscreen typically refers to what?

Answer 20

UVB rating

-best sunscreen uses both UVB and UVA protection