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Low concentrations of formaldehyde induce DNA damage and delay DNA repair after UV irradiation in human skin cells
Author(s) -
Emri Gabriella,
Schaefer Dirk,
Held Bjoern,
Herbst Christel,
Zieger Wolfgang,
Horkay Irene,
Bayerl Christiane
Publication year - 2004
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.0906-6705.2004.00157.x
Subject(s) - dna damage , comet assay , dna repair , nucleotide excision repair , microbiology and biotechnology , micronucleus test , dna , chemistry , keratinocyte , pyrimidine dimer , carcinogen , human skin , biochemistry , biology , in vitro , toxicity , genetics , organic chemistry
Long‐term occupational exposure to formaldehyde (FA) increases the risk for nasopharyngeal squamous cell carcinoma. As the skin is also in contact with FA by environmental exposure, we tested the genotoxic properties of appropriate low concentrations (<100 µM) of FA on cultured keratinocytes and fibroblasts of human skin. The initial DNA damage was assessed by comet assay. The induction of DNA protein crosslinks was measured by the ability of FA to reduce DNA migration induced by methyl‐methane‐sulfonate. Upon 4 h of exposure to FA, significant ( P < 0.05) crosslink formations were observed in fibroblasts (50 µM FA) and in keratinocytes (25 µM FA). Upon 8 h of exposure to FA (25 µM FA), significant crosslink formations were observed in both the cell types. FA is known to inhibit different DNA repair pathways. Therefore, we studied the effect of FA on UV‐induced repair. Human keratinocytes and fibroblasts exposed to 10 µM FA prior to UV irradiation showed disturbed repair kinetics after UVC and UVB, but not after UVA irradiation. Single‐strand breaks (SSBs) derived from nucleotide excision repair disappeared 6 h after solely UVC (3 mJ/cm 2 ) or 3 h solely UVB (30 mJ/cm 2 ) exposure in both the cell types. In the presence of FA, SSBs were still present at these time points containing a reference to a delay in DNA resynthesis/ligation. FA at a concentration not inducing micronuclei (12.5 µM) caused significant increase of UVC‐induced (4 mJ/cm 2 ) chromosomal damage. Proliferation of keratinocytes and fibroblasts was in parallel to observed DNA damages. In conclusion, our data suggest that environmental exposure to FA may contribute to UV‐induced skin carcinogenesis.