Upregulation of cellular NF-kappa B activity by alkylating carcinogens in human epidermal keratinocytes.

Abstract

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-kappaB was evaluated in human epidermal squamous cell carcinoma (SCC-13) keratinocytes in order to investigate the possible correlation of cellular NF-kappaB activity with chemical carcinogenesis. The activities of NF-kappaB induced by chemical carcinogens were determined in human SCC-13 keratinocytes transfected with pNF-kappaB-SEAP-NPT plasmid, permitting expression of the secretory alkaline phosphatase (SEAP) reporter gene in response to the NF-kappaB 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-kappaB activations in a time- and dose-dependent manner until 72 h, at concentrations of 0.5-5 microM. These results suggest that carcinogenicity by alkylating chemicals may be associated with the modulation of cellular NF-kappaB activity in human skin cells.

• Authors: Ki-Young Moon, Young Jong Lee, Yeong Shik Kim
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 26 Issue 8 Pg. 1195-7 (Aug 2003) ISSN: 0918-6158 [Print] Japan
• PMID: 12913277 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkylating Agents
• Carcinogens
• NF-kappa B

Topics

• Alkylating Agents (pharmacology)
• Carcinogens (pharmacology)
• Cell Line
• Dose-Response Relationship, Drug
• Epidermal Cells
• Epidermis (drug effects, metabolism)
• Humans
• Keratinocytes (drug effects, metabolism)
• NF-kappa B (biosynthesis, metabolism)
• Transfection (methods)
• Up-Regulation (drug effects, physiology)