N-Nitroso-N-methylurea
(Synonyms: 1-甲基-1-亚硝基脲,NMU; MNU; NMH) 目录号 : GC39498
N-Nitroso-N-methylurea（NMU; MNU; NMH）是一种有效的致癌剂，诱变剂和致畸剂。
Cas No.:684-93-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
Cell lines | SCC-13 cells |
Preparation Method | The transfectant human SCC-13 cells (2×104) cells were seeded in 96-well plates. When appropriate, the cells were washed with PBS and stimulated with medium containing 2 and 5µM of N-Nitroso-N-methylurea for 60min. At this time, the cells were treated with 4% fixing buffer (100µL) and quenching buffer (100µL), respectively and incubated for 20min at room temperature. Buffers were removed and the cells were washed twice with washing buffer(200µL). |
Reaction Conditions | 5µM; 60min |
Applications | Treatment of transfected keratinocytes with N-Nitroso-N-methylurea resulted in upregulation of NF-κB activity in cells, which was 38% higher than that in the control group. |
| Animal experiment [2]: | |
Animal models | Male albino Wistar rats |
Preparation Method | Male albino Wistar rats were equally randomized in to 2 groups of twelve animals each: Normal control rats (Group I) were fed with 1ml of citrate buffer(pH – 4.5) orally and normal saline (1ml/rat) thrice a week throughout the experiment (8 and 16wks. Cancercontrol rats (Group II) were administrated with N-Nitroso-N-methylurea(100mg/kg b.w.) in citrate buffer, pH – 4.5 and normal saline thrice in a week via intragastric route. Initially, N-Nitroso-N-methylurea was administered(n¼ 6) for a period of 8wk and then continued till 16wk(n¼ 6) to check the extent of carcinogenicity. |
Dosage form | 100mg/kg; p.o. |
Applications | N-Nitroso-N-methylurea-induced rats had significantly decreased body weight, water intake and food intake, increased serum gastrin levels, increased lipid peroxidation levels in gastric tissue, and decreased reduced glutathione levels. |
References: [1]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. [2]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. | |
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.
N-Nitroso-N-methylurea（NMU; MNU; NMH）是一种有效的致癌剂，诱变剂和致畸剂[1]。N-Nitroso-N-methylurea是一种直接作用的烷基化剂，与DNA相互作用[2]。N-Nitroso-N-methylurea靶向多种动物器官，以引起各种癌症和/或变性疾病[3]。N-Nitroso-N-methylurea也是一种重氮甲烷合成中的前体物质[4]。
在体外，N-Nitroso-N-methylurea（5µM）处理SCC-13细胞60min，显著升高了细胞内NF-κB活性，与对照组相比高出38%，还增加了I-κBα磷酸化的量[5]。
在体内，N-Nitroso-N-methylurea（100mg/kg）通过口服灌胃处理雄性白化病 Wistar大鼠16周，显著诱导了大鼠体重、饮水量和食物摄入量减少，升高了血清胃泌素和胃组织脂质过氧化水平，降低了还原型谷胱甘肽水平[6]。
| Cas No. | 684-93-5 | SDF | |
| 别名 | 1-甲基-1-亚硝基脲,NMU; MNU; NMH | ||
| Canonical SMILES | O=C(N)N(C)N=O | ||
| 分子式 | C2H5N3O2 | 分子量 | 103.08 |
| 溶解度 | DMSO: 125 mg/mL (1212.65 mM) | 储存条件 | 4°C, protect from light, stored under nitrogen |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 9.7012 mL | 48.506 mL | 97.012 mL |
| 5 mM | 1.9402 mL | 9.7012 mL | 19.4024 mL |
| 10 mM | 0.9701 mL | 4.8506 mL | 9.7012 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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Transnitrosation of non-mutagenic N-nitrosoproline forms mutagenic N-Nitroso-N-methylurea
Bioorg Med Chem 2015 Jul 1;23(13):3297-302.PMID:25975641DOI:10.1016/j.bmc.2015.04.058.
N-Nitroso-N-methylurea (NMU) is a potent carcinogen and suspected as a cause of human cancer. In this study, mutagenic NMU was detected by HPLC after the transnitrosation of non-mutagenic N-nitrosoproline (NP) to N-methylurea in the presence of thiourea (TU) under acidic conditions. The structure of NMU was confirmed by comparing (1)H NMR and IR spectra with that of authentic NMU after fractionation by column chromatography. Furthermore, a fraction containing NMU formed by transnitrosation was mutagenic in Salmonella typhimurium TA1535. NMU was formed in the reaction of NP and N-methylurea in the presence of 1,1,3,3-tetramethylthiourea (TTU) or 1,3-dimethylthiourea in place of TU as an accelerator. The reaction rate constants (k) for NMU formation were correlated with their nucleophilicity of sulfur atom in thioureas. The N-methylurea concentration did not affect the NMU formation, whereas the rate of NMU formation correlated linearly with concentrations of NP, TTU and oxonium ion. The observed kinetics suggests a mechanism by which the nitroso group was transferred directly from the protonated NP to the thiourea then to N-methylurea to form NMU. The rate-determining step was the formation of the complex with the protonated NP and thiourea.
N-Nitroso-N-methylurea elicits mammary cancer in resistant and sensitive rat strains
Proc Natl Acad Sci U S A 1981 Feb;78(2):1185-8.PMID:6785750DOI:10.1073/pnas.78.2.1185.
A single intravenous (i.v.) injection of the water-soluble mammary carcinogen N-Nitroso-N-methylurea (NMU; 35 mg/kg of body weight) elicited cancer of the breast in young female rats of two strains in the following incidence: Long-Evans strain, 4%; Sprague-Dawley strain, 70%. In sisters of these rats, a set of 5 i.v. injections of NMU (35 mg/kg at biweekly intervals) evoked mammary carcinoma as follows: Long-Evans strain, 76%; Sprague-Dawley strain, 100%. In its effectiveness in evoking mammary cancer in Sprague-Dawley rats, the lipid-soluble mammary carcinogen 7,8,12-trimethylbenz[a]anthracene exceeded NMU in rapidity of development of cancer and in tumor yield.
Effects of Lactofermented Beetroot Juice Alone or with N-Nitroso-N-methylurea on Selected Metabolic Parameters, Composition of the Microbiota Adhering to the Gut Epithelium and Antioxidant Status of Rats
Nutrients 2015 Jul 16;7(7):5905-15.PMID:26193312DOI:10.3390/nu7075260.
An objective of this work was to assess the biological activity of beetroot juice (Chrobry variety, Beta vulgaris L. ssp. vulgaris), which was lactofermented by probiotic bacteria Lactobacillus brevis 0944 and Lactobacillus paracasei 0920. The oxidative status of blood serum, kidneys, and liver of rats consuming the fermented beetroot juice were determined. The experimental rats were divided into four groups on diet type: Basal diet, basal diet supplemented with fermented beetroot juice, basal diet and N-Nitroso-N-methylurea treatment, and basal diet supplemented with fermented beetroot juice and N-Nitroso-N-methylurea treatment. Mutagen N-Nitroso-N-methylurea, which was added to diet in order to induce aberrant oxidative and biochemical processes and disadvantageous changes in the count and metabolic activity of the gut epithelium microbiota. The nutritional in vivo study showed that supplementing the diet of the rats with the lactofermented beetroot juice reduced the level of ammonia by 17% in the group treated with N-Nitroso-N-methylurea. Furthermore, the positive modulation of the gut microflora and its metabolic activity was observed in groups of rats fed with the diet supplemented with the fermented beetroot juice. A concomitant decrease in the b-glucuronidase activity was a consequence of the gut epithelium microbiota modulation. The antioxidant capacity of blood serum aqueous fraction was increased by about 69% in the group of rats treated N-Nitroso-N-methylurea mixed with the fermented beetroot juice and N-Nitroso-N-methylurea versus to the N-Nitroso-N-methylurea treatment, whereas the antioxidant parameters of the blood serum lipid fraction, kidneys, and liver remained unchanged.
Fluorometric determination of N-Nitroso-N-methylurea with nicotinamide and acetophenone
Anal Sci 2001 Mar;17(3):375-8.PMID:11990612DOI:10.2116/analsci.17.375.
A fluorometric method for the determination of N-Nitroso-N-methylurea (NMU) has been developed. It is based on the N-methylation reaction of nicotinamide with NMU and a subsequent condensation reaction with acetophenone, followed by an acid treatment to form a fluorescent 2,7-naphthyridine derivative. This method enabled the determination of NMU in the range 0.05 - 2 nmol/200 microl with a relative standard deviation of ca. 3%. It was applied to the determination of NMU formed from a precursor N-methylurea (MU) under simulated gastric conditions containing nitrite and thiocyanate ions at pH 3.0 in the presence of fresh orange juice and milk. NMU was extracted by an Extrelut 20 column and then determined. The mean recoveries of NMU added to the simulated gastric juice containing water, orange juice and milk were 86.5, 85.1 and 69.8%, respectively. The amounts of NMU formed from MU were found to decrease to below 25% in the presence of orange juice and milk.
N-nitroso-N-methylurea-induced rat mammary tumors arise from cells with preexisting oncogenic Hras1 gene mutations
Proc Natl Acad Sci U S A 1994 Apr 26;91(9):3749-53.PMID:8170982DOI:10.1073/pnas.91.9.3749.
GGA to GAA mutations in the 12th codon of the Hras gene are frequently observed in rat mammary tumors induced by N-Nitroso-N-methylurea (NMU). We developed an assay to measure point mutations present in tissues at a frequency of 10(-5) and have now applied this assay to measure the specific G to A transition of the Hras gene in rat mammary epithelium. We find that (i) 70% of untreated rats contain detectable levels of Hras mutants; (ii) these mutants are clustered within the gland as sectors in a manner consistent with their origin as a mutation arising during early organ development; and (iii) treatment with a carcinogenic dose of NMU did not result in a significant increase in the number of such mutants, the fraction of organ sectors with mutant cells, or the fraction of animals containing detectable levels of ras mutants. We conclude that the NMU-induced mammary tumors carrying the G to A transition at the 12th codon of the Hras gene arose from preexisting ras mutants and that an independent effect of NMU was directly or indirectly responsible for tumor formation.