UVR-Induced Changes
- High-frequency UVR results in DNA damage (mutations) and immunosuppression (local/systemic) – both steps key
to photocarcinogenesis
- DNA damage
- DNA considered chromophore for most biological effects from UVB and UVC
- Direct DNA damage via photoproducts, which are dimers formed by covalent bonding between adjacent pyrimidines
(cytosine or thymine) in same polynucleotide chain; if dimers unrepaired or incorrectly repaired, results in
mutation specific to UVB → cytosine changed to thymine (C to T), referred to as signature of UVB effect on DNA
- Cyclobutane-pyrimide dimers (CPD): most common DNA photoproduct; most frequent thymine-thymine (T-T)
> C-T > T-C and C-C
- 6,4-photoproduct: noncyclobutane dipyrimidine DNA photoproduct
- Indirect DNA damage from UVA likely via formation of reactive oxygen species (ROS)
- Immunosuppresion: ↓ number of Langerhans cells, modification of antigen-presenting cell capacity, release of
immunosuppressive cytokines (IL1, IL10, TNFα, etc.)
- DNA repair mechanisms
- Photoproducts repaired by nucleotide excision repair (NER) pathway (includes seven genetic complementation
groups and variant form)
- Post replication repair: damaged DNA ignored instead of repaired; replaced during replication but likely not very accurate
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