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N-nitroso-N-methylurea and N-nitroso-N-ethylurea Decrease in Nitric Oxide Production in Human Malignant Keratinocytes
Biomed. Sci. Lett. 2018;24:50-54
Published online March 31, 2018;  https://doi.org/10.15616/BSL.2018.24.1.50
© 2018 The Korean Society For Biomedical Laboratory Sciences.

Ki-Young Moon

BioMedicinal Chemistry Laboratory, Department of Clinical Pathology, Gwangju Health University, Gwangju 62287, Korea
Correspondence to: Ki-Young Moon. Department of Clinical Pathology, Gwangju Health University, Gwangju 62287, Korea. Tel: +82-62-958-7621, Fax: +82-62-958-7526, e-mail: kmoon@ghu.ac.kr
Received January 3, 2018; Revised March 5, 2018; Accepted March 6, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), direct alkylating chemical mutagens and carcinogens, are shown to be the upregulators of cellular NF-κB, regulating various genes that mediate tumorigenesis and carcinogenesis. Nitric oxide (NO), a toxic reactive radical gas, has been known to induce programmed cell death or apoptosis in various cells. Therefore, the assessment of NO production was examined to elucidate the possible contribution of NO release to the chemical carcinogenic potency of NMU and NEU in human skin cells. NMU and NEU did not alter the NO production, but they caused a significant downregulation of the NO generation on lipopolysaccharide (LPS)-induced NO production at concentrations ranging from 2~5 μM. The degree of downregulation of NO by NMU and NEU decreased up to 15% and 20%, respectively, compared to the control. These results demonstrate that the LPS-inducible keratinocytes NO synthase is involved in modulating carcinogenic potency by NMU and NEU, and the regulation of the cellular NF-κB activity by NMU and NEU is negatively correlated with the level of LPS-induced NO production in human skin cells. The findings of this study suggest the hypothesis that NMU and NEU-induced carcinogenesis may be associated with the downregulation of NO production, and the inducible NO may play an important role in NMU and NEU-induced carcinogenicity in human epidermal keratinocytes.
Keywords : Chemical carcinogenesis, NMU and NEU, NF-κB activity, Nitric oxide, Human malignant keratinocytes