Low concentrations of formaldehyde induce DNA damage and delay DNA repair after UV irradiation in human skin cells.
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 microM) 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 microM FA) and in keratinocytes (25 microM FA). Upon 8 h of exposure to FA (25 microM 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 microM 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/cm2) or 3 h solely UVB (30 mJ/cm2) 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 microM) caused significant increase of UVC-induced (4 mJ/cm2) 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.
Emri
Gabriella
G
Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
Schaefer
Dirk
D
Held
Bjoern
B
Herbst
Christel
C
Zieger
Wolfgang
W
Horkay
Irene
I
Bayerl
Christiane
C
D000328:Adult; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D019457:Chromosome Breakage; D003043:Cocarcinogenesis; D020552:Comet Assay; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D005557:Formaldehyde / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D015162:Micronucleus Tests; D008856:Microscopy, Fluorescence; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology; D014466:Ultraviolet Rays
D005557:Formaldehyde; D004247:DNA; D008741:Methyl Methanesulfonate