Nucleotide excision repair genes are upregulated by low-dose artificial ultraviolet B: evidence of a photoprotective SOS response?
Nucleotide excision repair is a major mechanism of defense against the carcinogenic effects of ultraviolet light. Ultraviolet B causes sunburn and DNA damage in human skin. Nucleotide excision repair has been studied extensively and described in detail at the molecular level, including identification of many nucleotide excision repair-specific proteins and the genes encoding nucleotide excision repair proteins. In this study, normal human keratinocytes were exposed to increasing doses of ultraviolet B from fluorescent sunlamps, and the effect of this exposure on expression of nucleotide excision repair genes was examined. An RNase protection assay was performed to quantify transcripts from nucleotide excision repair genes, and a slot blot DNA repair activity assay was used to assess induction of the nucleotide excision repair pathway. The activity assay demonstrated that cyclobutane pyrimidine dimers were removed efficiently after exposure to low doses of ultraviolet B, but this activity was delayed significantly at higher doses. All nucleotide excision repair genes examined demonstrated a similar trend: ultraviolet B induces expression of nucleotide excision repair genes at low doses, but downregulates expression at higher doses. In addition, we show that pre-exposure of cells to low-dose ultraviolet protected keratinocytes from apoptosis following high-dose exposure. These data support the notion that nucleotide excision repair is induced in cells exposed to low doses of ultraviolet B, which may protect damaged keratinocytes from cell death; however, exposure to high doses of ultraviolet B downregulates nucleotide excision repair genes and is associated with cell death.
Maeda
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Department of Laboratory Medicine and Pathology, University of Alberta, Faculty of Medicine, Mackenzie Health Science Center, Edmonton, Canada.
Chua
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Chong
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Sim
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Nikaido
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D017209:Apoptosis / Q000528:radiation effects; D002478:Cells, Cultured; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects*; D019281:Dimerization; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000528:radiation effects; D013941:Thymine / Q000737:chemistry; D014158:Transcription, Genetic / Q000528:radiation effects; D014466:Ultraviolet Rays
D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D013941:Thymine