Upregulation of Cellular NF-κB Activity by Alkylating Carcinogens in Human Epidermal Keratinocytes

Effect of alkylating carcinogens, i.e., N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), as well as the simpler alkylating agents, methyl iodide and ethyl iodide, on the activation of NF-κB was evaluated in human epidermal squamous cell carcinoma (SCC-13) keratinocytes in order to inves...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2003, Vol.26(8), pp.1195-1197
Main Authors: Moon, Ki-Young, Lee, Young Jong, Kim, Yeong Shik
Format: Article
Language:English
Subjects:
Alkylating Agents - pharmacology
alkylating carcinogen
Analytical, structural and metabolic biochemistry
Biological and medical sciences
Carcinogens - pharmacology
Cell Line
Dose-Response Relationship, Drug
Epidermal Cells
Epidermis - drug effects
Epidermis - metabolism
Fundamental and applied biological sciences. Psychology
Humans
Keratinocytes - drug effects
Keratinocytes - metabolism
Medical sciences
NF-kappa B - biosynthesis
NF-kappa B - metabolism
NF-κB
Pharmacology. Drug treatments
SCC-13 keratinocyte
Transfection - methods
Up-Regulation - drug effects
Up-Regulation - physiology
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Summary:Effect of alkylating carcinogens, i.e., N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), as well as the simpler alkylating agents, methyl iodide and ethyl iodide, on the activation of NF-κB was evaluated in human epidermal squamous cell carcinoma (SCC-13) keratinocytes in order to investigate the possible correlation of cellular NF-κB activity with chemical carcinogenesis. The activities of NF-κB induced by chemical carcinogens were determined in human SCC-13 keratinocytes transfected with pNF-κB-SEAP-NPT plasmid, permitting expression of the secretory alkaline phosphatase (SEAP) reporter gene in response to the NF-κB activity and contains the neomycin phosphotransferase (NPT) gene conferring resistance to the geneticin. In this cell-based assay system, all alkylating carcinogens significantly upregulated the cellular NF-κB activations in a time- and dose-dependent manner until 72 h, at concentrations of 0.5—5 μM. These results suggest that carcinogenicity by alkylating chemicals may be associated with the modulation of cellular NF-κB activity in human skin cells.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.26.1195