Upregulation of cellular NF-kappa B 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-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.
Moon
Ki-Young
KY
Department of Clinical Pathology, and Bioindustry and Technology Research Institute, Kwangju Health College, Kwangju, Japan. kmoon@www.kjhc.ac.kr
Lee
Young Jong
YJ
Kim
Yeong Shik
YS
D000477:Alkylating Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D000477:Alkylating Agents; D002273:Carcinogens; D016328:NF-kappa B