In human malignant keratinocytes, N-nitroso-N-methylurea (NMU; 5 μM) therapy promotes cellular NF-κB activity. I-κBα phosphorylation is also increased by N-nitroso-N-methylurea [5].

Tumor models can be created in animals by using N-nitroso-N-methylurea.

Absorption, Distribution and Excretion
The high chemical reactivity of NMU renders it unlikely that enzymic catalysis is involved in its decomposition. NMU is a direct alkylating agent and alkylates nucleic acids both in vitro and in vivo. Such alkylation has been detected in a number of tissues, including brain, lung, kidney, liver, intestine, thymus and spleen, in a number of species, including mice, rats, hamsters and mini-pigs. All three hydrogen atoms in the methyl group of NMU are retained in the methylated nucleosides formed in nucleic acids after alkylation by NMU in vivo.

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Metabolism / Metabolites
The cyanate ion produced by decomposilion of NMU at physiological pH can react with proteins by carbanoylation.
In vivo formation of NMU was shown by methylation of guanine at N7 after feeding of the precursors methylurea and sodium nitrite. /Species not specified/

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Biological Half-Life
NMU was not detected in the blood of rats 15 minutes after an i.v. injection of 100 mg/kg bw.

Toxicity Summary
IDENTIFICATION AND USE: N-Nitroso-N-methylurea (NMU) is a solid. NMU was once widely used to synthesize diazomethane in the laboratory, it has been replaced by other reagents for this use. NMU has been studied as a chemotherapeutic agent in cancer treatment, either alone or in combination with cyclophosphamide. Small quantities are used in research to study its mutagenic effects on plants. HUMAN STUDIES: Nausea and vomiting were seen after iv injection of 4 mg/kg body wt NMU to patients. NMU produced mutations in human lymphoblast cell line TK6. The malignant transformation of adult human prostate epithelial cells has been reported after multiple exposures to the NMU. ANIMAL STUDIES: The major toxic effects of NMU in animals result from severe damage to hematopoietic, lymphoid and other tissues that have rapid rates of cell turnover. Acute treatment with NMU has been shown to inhibit protein and nucleic acid synthesis in tissues. NMU acutely induced rod-dominant photoreceptor degeneration in monkey retinas, but the photoreceptor function was impaired in both the rods and cones. The intraperitoneal application of NMU led to moderate systemic side effects in mice and to selective photoreceptor degeneration. Intravitreal injections of NMU also induced photoreceptor degeneration; however, no systemic side effects were observed. In rabbits, the intravitreal injection of 3 mg/kg bw MNU leads to selective but inhomogeneous photoreceptor degeneration. Carcinomas of the forestomach were seen in rats at doses of 10 mg/kg bw given once every 2 weeks and 20 mg/kg bw given once every 4 weeks over a period of 9 months. Malignant tumors of the brain (sarcomas, gliomas) and the peripheral nervous system (described as neurosarcomas) were also observed. Odontogenic neoplasms were found in 2/10 rats after a single i.g. administration of 90 mg/kg bw. Minipigs received 10 mg/kg bw NMU at fortnightly intervals for 4.5 years. All of the 9 animals that lived 50 months developed benign and some malignant tumors of the stomach. Three species of monkeys, Macaca mulatta, M. fascicularis and Cercopithecus aethiops were administered NMU orally, and were found to have squamous-cell carcinomas of the oropharynx and/or esophagus. One skin application of 50-100 mg/kg bw to 125 newborn mice induced mainly lymphatic leukemias in about 50% of treated animals. Application of a 0.5% solution of NMU 3 times/week for 30 weeks (1.75 mg/dose) to rats produced multiple squamous- and basal-cell carcinomas of the skin in 9/9 animals. The first tumor appeared at 20 weeks. Skin application to 20 Syrian golden hamsters with 0.5% solution of NMU 3 times/week for 13 weeks (0.35 mg/dose) produced squamous-cell carcinomas of skin in 18/18 animals, the first tumor appearing at 8 weeks. Tumors of the nervous system and kidney were observed in the offspring of rats treated with NMU during the last third of pregnancy. Mammary tumors also occurred in the treated mothers. Congenital defects in the offspring of mice following paternal treatment with NMU also occurred. A model of retinal degeneration has been developed in mice using NMU. In mice, ectrodactyly was the predominant effect after treatment on day 11 of pregnancy. Treatment on day 12 triggered especially double-sided microdactyly. The genetic activity of NMU has been demonstrated in bacterial phage, Escherichia coli, Salmonella typhimurium, Saccharomyces cerevisiae, Serratia marcescens, Chinese hamster cells and Drosophila melanogaster, inducing forward and reverse mutations and gene conversions.

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Interactions
Rats were pretreated for a number of weeks with ... N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea ... . A subsequent challenge with a single, low-dose of radioactivity labeled dimethylnitrosamine was given to assay the capacity of the liver for O6-methlyguanine repair. ... Pretreatment for 2 weeks with N-ethyl-N-nitrosourea resulted in strongly enhanced O6-methylguanine repair, as did a similar pretreament with diethylnitrosamine, which was included as a positive control. The same pretreatment scheme which was highly effective in the case of N-ethyl-N-nitrosourea, was found to be totally ineffective in the case of N-methyl-N-nitrosourea. When N-methyl-nitrosourea was admin for 8 wk instead of 2, a small but statistical incr in O6-methylguanine repair was observed. ... Two factors are responsible for the low effectivity of N-methyl-nitrosourea. The first is the relatively low extent of liver DNA methylation by this cmpd when compared with dimethylnitrosoamine. The second is the low efficiency of methylating agents to induce O6-ethylating agents. ... It is concluded that the capacity of an agent to enhance O6-methylguanine repair in rat liver ... reflects the hepato(co)carcinogenic capacity of that agent.
The administration of nicotine during the perinatal stages of life resulted in a significant decrease in tumors occurring after transplacental induction by NMU. The overall tumor incidence following po application of NMU to dams was 85% in rats of the F1-generation, the main occurrence being related to the neurogenic system. Regular injections of nicotine before or after birth resulted in a reduction of malignancies by 17% and 22%, resp. ... These findings suggest that nicotine is capable of modulating the expression of chemically induced tumors of the neurogenic system in a favorable way.
MNU applied to fertilized egg cells /of Oryza sativa L/ induced an increased range of variation for aluminum tolerance in M2. For the M3, the induced variability in M2 was heritable; 50 variants expressed different degrees of tolerance for aluminum toxicity, some of which did not show growth inhibition even at 30 ppm aluminum. Tolerance for aluminum toxicity and longer root development were interrelated.
Ellagic acid ... inhibits the activity of the direct-acting mutagen N-methyl-N-nitrosourea in Salmonella typhimurium TA100. Ellagic acid at 0.10, 0.25, 0.50, and 1.0 mM inhibited the mutagenicity of N-methyl-N-nitrosourea (0.40 mM) by 3, 13, 45, and 60%, respectively ... Ellagic acid inhibition of N-methyl-N-nitrosourea induced mutagenicity is due to specific inhibition of methylation at the O6 position of guanine through an ellagic acid-duplex DNA affinity-binding mechanism.
For more Interactions (Complete) data for N-Nitroso-N-methylurea (18 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 110 mg/kg bw
LD50 Rat iv 110 mg/kg bw
LD50 Hamster sc 110 mg/kg bw
LD50 Hamster sc 50 mg/kg bw
For more Non-Human Toxicity Values (Complete) data for N-Nitroso-N-methylurea (6 total), please visit the HSDB record page.

[1]. N-nitrosomethylurea as mammary gland carcinogen in rats. J Natl Cancer Inst. 1975 Feb;54(2):401-14.

[2]. Review: Animal models of N-Methyl-N-nitrosourea-induced mammary cancer and retinal degeneration with special emphasis on therapeutic trials. In Vivo. 2011 Jan-Feb;25(1):11-22.

[3]. Effects of N-nitroso-N-methylurea on enzymatic ontogeny associated with teratogenesis. Teratology. 1968 May;1(2):179-91.

[4]. One-pot synthesis of α-haloketones employing a membrane-based semibatch diazomethane generator. Journal of Flow Chemistry volume 6, pages211-217(2016).

[5]. Moon KY. N-nitroso-N-methylurea and N-nitroso-N-ethylurea induce upregulation of cellular NF-kappa B activity through protein kinase C-dependent pathway in human malignant keratinocytes. Arch Pharm Res. 2010 Jan;33(1):133-9.

[6]. Palliative Role of Aqueous Ginger Extract on N-Nitroso-N-Methylurea-Induced Gastric Cancer. Nutr Cancer. 2020;72(1):157-169.

[7]. Effect of Crocin on Cell Cycle Regulators in N-Nitroso-N-Methylurea-Induced Breast Cancer in Rats. DNA Cell Biol. 2015 Nov;34(11):684-91.

N-Nitroso-N-methylurea can cause cancer according to an independent committee of scientific and health experts.
N-nitroso-n-methylurea appears as pale yellow crystals or light yellow moist powder. (NTP, 1992)
N-methyl-N-nitrosourea is a member of the class of N-nitrosoureas that is urea in which one of the nitrogens is substituted by methyl and nitroso groups. It has a role as a carcinogenic agent, a mutagen, a teratogenic agent and an alkylating agent.
N-Nitroso-n-methylurea has been studied in mutagenicity and genetics studies and for use as a cancer chemotherapy agent. No commercial use of N-nitroso-n-methylurea is known. Acute (short-term) exposure toN-nitroso-n-methylurea in humans causes dermatitis. No information is available on the chronic (long-term), reproductive, developmental, or carcinogenic effects of N-nitroso-n-methylurea in humans or animals. Tumors have been reported in the offspring of animals treated with N-nitroso-n- methylurea during their pregnancy. Animal studies have reported tumors of the brain, spinal cord, nerves, stomach, pancreas, and kidneys from oral exposure to N-nitroso-n-methylurea. EPA has classified N- nitroso-n-methylurea as a Group B2, probable human carcinogen.
Methylnitrosourea is a pale yellow, crystalline nitrosourea that is sensitive to light and moisture and emits toxic fumes of nitrogen oxides when heated to decomposition. Methylnitrosourea is an alkylating agent that is primarily used for research purposes to induce tumors and has also been studied as a chemotherapy agent for cancer treatment. Exposure to methylnitrosourea causes dermatitis. Methylnitrosourea is reasonably anticipated to be a human carcinogen. (NCI05)
A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.

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Mechanism of Action
The role of oncogene ras in carcinogen-induced neoplastic transformation was examined. Rat mammary carcinomas induced by N-nitroso-N-methylurea and 7,12-dimethylbenzanthracene showed mutations in codons 12 and 61, resp, of the gene H-ras-1. The mutation at codon 12 was a guanine-guanine-adenine to guanine-adenine-adenine transition.

C₂H₅N₃O₂

103.08

103.038

684-93-5

12699

Off-white to light brown solid powder

1.5±0.1 g/cm3

164.3±23.0 °C at 760 mmHg

119-124°C

53.1±22.6 °C

2.0±0.3 mmHg at 25°C

1.545

-0.03

1

3

0

7

90.9

0

ZRKWMRDKSOPRRS-UHFFFAOYSA-N

InChI=1S/C2H5N3O2/c1-5(4-7)2(3)6/h1H3,(H2,3,6)

1-methyl-1-nitrosourea

NNitrosoNmethylurea; N Nitroso N methylurea

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~2425.30 mM)` H2O : ~50 mg/mL (~485.06 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (20.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (20.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (20.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10 mg/mL (97.01 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)