''N''-Nitroso-''N''-methylurea (NMU) is a highly reliable

carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...

mutagen In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer i ...

, and teratogen. NMU is an

alkylating agent Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...

, and exhibits its toxicity by transferring its

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ...

group to

nucleobases Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the bas ...

nucleic acids Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...

, which can lead to AT:GC transition mutations. NMU is the traditional precursor in the synthesis of

diazomethane Diazomethane is the chemical compound CH2N2, discovered by German chemist Hans von Pechmann in 1894. It is the simplest diazo compound. In the pure form at room temperature, it is an extremely sensitive explosive yellow gas; thus, it is almost ...

. It has the potentially advantageous property that the stoichiometric byproducts formed are water, carbon dioxide, and ammonia, which are innocuous or easily removed. However, because it is unstable at temperatures beyond 20 °C and somewhat shock-sensitive, it has become obsolete for this purpose and replaced by other N-nitroso compounds: (''N''-methyl)nitrosamides and

nitrosamine In organic chemistry, nitrosamines (or more formally ''N''-Nitrosamines) are organic compounds with the chemical structure , where R is usually an alkyl group. They feature a nitroso group () bonded to a deprotonated amine. Most nitrosamines a ...

s. Most chemical supply houses have stopped carrying it. Acute exposure to NMU in humans can result in skin and eye irritation, headache, nausea, and vomiting.Hazardous Substance Fact Sheet for NMU
New Jersey Department of Health and Senior Services NMU is ''reasonably anticipated to be a human carcinogen'' based on sufficient evidence of carcinogenicity in experimental animals (

IARC IARC may refer to: * International Aerial Robotics Competition * International Age Rating Coalition * International Agency for Research on Cancer * International Arctic Research Center * Israel Amateur Radio Club The Israel Amateur Radio Club ...

1972, 1978, 1987).NMU Substance Profile
NTP, Report on Carcinogens, Eleventh Edition Various cancers induced in animal models include: squamous cell

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoderm ...

s of the forestomach,

sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal ( connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sar ...

s and

glioma A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours. Signs and symptoms ...

s of the brain,

adenocarcinoma Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, o ...

s of the pancreas, mammary carcinomas,

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

, and

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include en ...

s. However, the actual potential for human exposure is quite limited, as the chemical is not produced or used in large quantities NMU is teratogenic and embryotoxic, resulting in craniofacial (

cleft palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The ...

) and skeletal defects, fetal growth retardation, and increased

fetal resorption Fetal resorption (also known as fetus resorption) is the disintegration and assimilation of one or more fetuses in the uterus at any stage after the completion of organogenesis, which, in humans, is after the ninth week of gestation. Before organog ...

.Wada, A., et al. (1994). Induction of Congenital Malformations in Mice by Paternal Methylnitrosourea Treatment. Congenital Anomalies 34:65-70.Nagao, T., et al. (1991). Induction of Fetal Malformations After Treatment of Mouse Embryos with Methylnitrosourea at the Preimplantation Stages. Teratogenesis, Carcinogenesis, and Mutagenesis 11:1-10.Faustman, E., et al. (1989). ''In Vitro'' Developmental Toxicity of Five Direct-Acting Alkylating Agents in Rodent Embryos: Structure-Activity Patterns. Teratology 40:199-210. Exposure to NMU during pre-implantation, post-implantation, organogenesis, or by paternal exposure can result in these effects.

References

External links

* {{DEFAULTSORT:Nitroso-N-methylurea, N- Carcinogens Embryotoxicants IARC Group 2A carcinogens Male-mediated teratogens Mutagens Nitrosamines Nitrosoureas Teratogens Ureas Methylating agents