Solar radiation, sunscreen, vit D

Question 1

Ranges of UV

Answer 1

• UVB (causes sunburns, direct DNA damage): 290-320nm
• UVA (causes majority of skin aging, damage to dermis): 320-400 nm
• UVB is completely absorbed by epidermis, UVA gets to dermis

Question 2

DNA damage from UVB

Answer 2

• Causes direct DNA damage
• UVB photon absorbed by DNA, breaks hydrogen bond btwn pyrimidine and purine mate
• Pyrimidine will bind to an adjacent pyrimidine (only C and T, but any combo) on the same DNA strand (covalent bond) and form a cyclobutane pyrimidine dimer (CPD) or a 6,4 photoproduct
• 6,4 photoproduct is more rare, but more mutagenic
• Either type changes DNA strand conformation (induces bulge) and prevents transcription

Question 3

DNA damage from UVA

Answer 3

• Causes indirect DNA damage: formation of ROS
• Too many ROS and cell enters state of oxidative stress (overwhelms natural antioxidants)
• Can lead to oxidation of DNA and double or single stranded breaks, also oxidation of lipids
• Oxidation of some lipids leads to formation of malondialdehyde (MDA) which forms a covalent bond w/ guanosine (DNA adduct: 8-hydroxyguanosine)
• This also silences the gene until repaired

Question 4

Repair of DNA damage

Answer 4

• Damage from both UVB and UVA usually repaired in same way
• NER (nucleotide excision repair), which uses other strand as template
• NER is error prone and may add the wrong base, causing mutation
• Damage is repairable but mutations aren’t
• p53 binds to DNA at CPDs and initiates repair, while holding the cell in arrest until repaired
• If damage is too substantial p53 initiates apoptosis
• p53 gene can be mutated due to UV damage (very susceptible)

Question 5

Production of melanin

Answer 5

• Increased in response to sun damage
• p53 induces production of melanocyte stimulating hormone (MSH) in keratinocytes, which is released onto melanocytes to produce more melanin
• Melanin is produced in melanosomes via tyrosinase (requires Cu), extended from melanocyte to keratinocytes (30)
• Tyrosine-> dopamine->-> melanin
• Melanin migrates to areas above the nucleus in keratinocytes to protect them from UV
• Eumelanin (normal, brown) is excellent broad spectrum UV absorber
• Phleomelanin (more in gingers) is not a good UV absorber and can produce ROS

Question 6

Sunscreen

Answer 6

• SPF (sun protection factor): how long it takes the skin to burn w/ sunscreen divided by how long it takes w/o sunscreen
• SPF is a surrogate for UVB attenuation (b/c only UVB causes burns)
• Should put on 1 table spoon (5ml) of sunscreen for each part of body
• Broad spectrum = at least SPF 15 and critical wavelength (90% of UV has been absorbed) must be over 370nm

Question 7

Types of sun filters

Answer 7

• Organic (chemical): avobenzone, only filters UVA
• Inorganic (physical): zinc (filters both UVA and UVB), titanium (filters UVB only). Large particles will reflect light
• Inorganic nanoparticles absorb light, do not reflect (generate ROS), but are not absorbed into skin
• Alterations to filters: isomers inactivate, ROS can inactivate

Question 8

Vit D

Answer 8

• Precursor is 7-DHC, upon irradiation of UVB it is converted to vit D (cholecalciferol)
• Vit D is hydroxylated in liver to 25OHD (measured to test vit D levels)
• 25OHD is converted to 1,25OH2D in kidney or skin (keratinocytes), can be upregulated in response to injury or infection
• 1,25OH2D (active form) triggers keratinocytes to produce anitmicrobial peptides (cathelicidins)
• Active vit D controls over 200 genes
• Vit D deficiency can cause rickets in children and osteomalacia in adults
• RDA for adults: 600 (800 for elderly, 400 for infants), want 20ng/ml blood concentration