PMID- 10461458
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20061115
IS  - 0031-8655 (Print)
IS  - 0031-8655 (Linking)
VI  - 70
IP  - 2
DP  - 1999 Aug
TI  - The soluble eumelanin precursor 5,6-dihydroxyindole-2-carboxylic acid enhances 
      oxidative damage in human keratinocyte DNA after UVA irradiation.
PG  - 191-8
AB  - Soluble melanin precursors are present in serum and may act as skin chromophores 
      contributing to UVR-induced oxidative damage. Our study aimed to determine 
      whether the soluble eumelanin precursor 5,6-dihydroxy-indole-2-carboxylic acid 
      (DHICA) photosensitizes DNA damage in human keratinocytes exposed to UVA 
      irradiation. The HaCaT keratinocytes were incubated with and without DHICA, 
      before irradiation with broadband UVA (320-400 nm). The DNA photodamage was 
      assessed using the comet assay that detects frank single-strand breaks (SSB) and 
      specific oxidative lesions with the addition of endonuclease III. Without DHICA 
      incubation, there was no significant increase in SSB, compared to unirradiated 
      cells, for doses up to 48.5 J/cm2 (< 1 minimum erythemal dose). Preincubation 
      with 0.5 microM DHICA caused an increase in SSB at every UVA dose (significant 
      from 12.1 to 48.5 J/cm2), while varying the DHICA concentration (0.125-2 microM) 
      showed this effect to be concentration dependent such that SSB increased and 
      endonuclease III-sensitive sites decreased with increasing DHICA concentration. 
      The irradiation of cells in the presence of antioxidants (catalase, mannitol and 
      histidine) suggests that DHICA-induced photosensitization is mediated via singlet 
      oxygen and, to a lesser extent, hydroxyl radicals. These results indicate that 
      DHICA can induce strand breaks with UVA at clinically relevant doses via a 
      mechanism involving reactive oxygen species.
FAU - Kipp, C
AU  - Kipp C
AD  - Department of Photobiology, St John's Institute of Dermatology, Guy's King's 
      School of Medicine, King's College London, University of London, UK.
FAU - Young, A R
AU  - Young AR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Photochem Photobiol
JT  - Photochemistry and photobiology
JID - 0376425
RN  - 0 (Antioxidants)
RN  - 0 (Indoles)
RN  - 4790-08-3 (5,6-dihydroxy-2-indolylcarboxylic acid)
SB  - IM
MH  - Antioxidants/pharmacology
MH  - Cell Line
MH  - Cells, Cultured
MH  - *DNA Damage
MH  - Humans
MH  - Indoles/*toxicity
MH  - Keratinocytes/drug effects/radiation effects
MH  - Oxidation-Reduction
MH  - Photobiology
MH  - Ultraviolet Rays/adverse effects
EDAT- 1999/08/26 00:00
MHDA- 1999/08/26 00:01
CRDT- 1999/08/26 00:00
PHST- 1999/08/26 00:00 [pubmed]
PHST- 1999/08/26 00:01 [medline]
PHST- 1999/08/26 00:00 [entrez]
PST - ppublish
SO  - Photochem Photobiol. 1999 Aug;70(2):191-8.