N-Nitroso-N-methylurea (NMU; MNU; NMH) is a potent carcinogen, mutagen and teratogen[1]. N-Nitroso-N-methylurea is a direct-acting alkylating agent that interacts with DNA[2]. N-Nitroso-N-methylurea targets multiple animal organs to cause various cancers and/or degenerative diseases[3]. N-Nitroso-N-methylurea is also a precursor in the synthesis of diazomethane[4].
In vitro, treatment of SCC-13 cells with N-Nitroso-N-methylurea (5µM) for 60 min significantly increased intracellular NF-κB activity by 38% compared to the control group and also increased the amount of I-κBα phosphorylation[5].
In vivo, oral administration of N-Nitroso-N-methylurea (100mg/kg) to male albino Wistar rats for 16 weeks significantly induced a decrease in body weight, water intake, and food intake, increased serum gastrin and gastric tissue lipid peroxidation levels, and decreased reduced glutathione levels [6].
References:
[1] Lawley P D. N-nitroso compounds[M]//Chemical carcinogenesis and mutagenesis I. Berlin, Heidelberg: Springer Berlin Heidelberg, 1990: 409-469.
[2] Likhachev A J, Ivanov M N, Brésil H, et al. Carcinogenicity of single doses of N-nitroso-N-methylurea and N-nitroso-N-ethylurea in Syrian golden hamsters and the persistence of alkylated purines in the DNA of various tissues[J]. Cancer Research, 1983, 43(2): 829-833.
[3] Tsubura A, Lai Y C, Miki H, et al. Animal models of N-methyl-N-nitrosourea-induced mammary cancer and retinal degeneration with special emphasis on therapeutic trials[J]. In Vivo, 2011, 25(1): 11-22.
[4] Hecht S M, Kozarich J W. Mechanism of the base-induced decomposition of N-nitroso-N-methylurea[J]. The Journal of Organic Chemistry, 1973, 38(10): 1821-1824.
[5] Moon K Y. N-nitroso-N-methylurea and N-nitroso-N-ethylurea induce upregulation of cellular NF-κ B activity through protein kinase C-dependent pathway in human malignant keratinocytes[J]. Archives of pharmacal research, 2010, 33(1): 133-139.
[6] Mansingh D P, Pradhan S, Biswas D, et al. Palliative role of aqueous ginger extract on N-nitroso-N-methylurea-induced gastric cancer[J]. Nutrition and cancer, 2020, 72(1): 157-169.