N -ethyl- N -nitrosourea

Structural formula
General
Surname	N -ethyl- N -nitrosourea
other names	ENU; Ethyl nitrosourea; 1-ethyl-1-nitrosourea;
Molecular formula	C 3 H 7 N 3 O 2
External identifiers / databases
EC number	212-072-2
ECHA InfoCard	100.010.975
PubChem	12967
Wikidata	Q287629
properties
Molar mass	117.11 g mol −1
safety instructions
H and P phrases	H: 301-312-332-350-360
	P: 201-280-301 + 310-308 + 313
Toxicological data	300 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

N -Ethyl- N -nitrosourea , often referred to as ethylnitrosourea and mostlyabbreviatedas ENU (= ethyl nitroso urea ), is a compound from the group of nitrosoureas . It is a powerful carcinogen and highly potent mutagen .

properties

ENU is a highly reactive compound that is sensitive to moisture and light. Storage is usually carried out at temperatures below −10 ° C. The compound is about 1.3% soluble in water. The octanol-water partition coefficient (log K _OW ) is 0.23.

The stability of aqueous solutions depends on the pH value . At room temperature and pH 4.0, the half-life in water is 190 hours. At pH 6.0 only 31 hours, at pH 7.0 1.5 hours, at pH 8.0 six minutes and at pH 9.0 three minutes. ENU decomposes to diazoethane in alkaline solutions . Nitrogen oxides are produced during thermal decomposition . Ethyl nitrosourea is an alkylating agent that can transfer its ethyl group to nucleobases - mostly thymine - of the DNA in the cell nucleus . This property makes this compound on the one hand a strong carcinogen (a substance that can cause cancer ), on the other hand, with ethylnitrosourea, ENU generates tumors in various organs, depending on the type of application and the application site. For example, subcutaneous injection in rats leads to liver cancer , hepatocellular carcinoma , adenocarcinoma in the lungs , lymphomas and tumors of the peripheral nervous system , the spinal cord and the brain . Oral administration mainly leads to tumors of the nervous system. Intraperitoneal injections induce malignant tumors in the liver , kidneys , ovaries , lungs and stomach , among other things . Leukemia , gliomas and tumors of the uterus and vagina develop intravenously .

ENU also alkylates the spermatogonium , the stem cell population in the germinal epithelium of the testicle

use

There is no technical use for ethylnitrosourea due to its instability and high toxicity. It is produced on a laboratory scale in small quantities. The first synthesis took place in 1919.

In biochemical research, ENU has been used to induce mutations since the early 1970s. In this application it is also referred to as “super mutagen”. The transfer of the ethyl group to the nucleobases is irreversible. This alkylation can lead to mismatches in the complementary strand of DNA during replication . The mismatches essentially cause point mutations ( adenine → thymine ). The point mutations can be brought into the germline through the spermatogonium (germline mutation).

The mutation rate is around 1 per 1000 base pairs.

Individual evidence

↑ ^a ^b ^c data sheet N-Nitroso-N-ethylurea from Sigma-Aldrich , accessed on April 12, 2011 ( PDF ).
↑ C. Hansch et al: Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. American Chemical Society, 1995, p. 6.
↑ IARC ; Some Inorganic Substances, Chlorinated Hydrocarbons, Aromatic Amines, N-Nitroso Compounds and Natural Products. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans. 1972.
^ IARC: Some N-Nitroso Compounds. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans. 1978.
↑ Entry on N-NITROSO-N-ETHYLUREA in the Hazardous Substances Data Bank , accessed on July 27, 2012.
↑ WL Russell et al .: Dose-response curve for ethylnitrosourea-induced specificlocus mutations in mouse spermatogonia. In: PNAS 79, 1982, pp. 3589-3591. PMID 6954505
^ WL Russell et al .: Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. In: PNAS 76, 1979, pp. 5818-5819. PMID 293686
↑ C. Meyer: Phenotypic and metabolic physiological characterization of ENU (ethylnitrosourea) induced mouse mutants with impaired body weight regulation Dissertation, Philipps University Marburg, 2005.
↑ JK Noveroske include: The mutagenic action of N-ethyl-N-nitrosourea in the mouse. In: Mamm Genome 11, 2000, pp. 478-483, PMID 10886009 .
↑ EM Rinchik: Chemical mutagenesis and fine-structure functional analysis of the mouse genome. In: Trends Genet 7, 1991, pp. 15-21, PMID 2003334 .

↑ JS Weber et al.: Optimal N-ethyl-N-nitrosourea (ENU) doses for inbred mouse strains. In: Genesis 26, 2000, pp. 230-233, PMID 10748459 .

literature

T. Murota and T. Shibuya: The induction of specific-locus mutations with N-propyl-N-nitrosourea in stem-cell spermatogonia of mice. In: Mutat Res 264, 1991, pp. 235-240, PMID 1723506 .
T. Murota and T. Shibuya: A review of the genotoxicity of 1-ethyl-1-nitrosourea. In: Mutat Res 297, 1993, pp. 3-38, PMID 7686271 .
MJ Lee et al .: Characteristics of ethylnitrosourea-induced cataracts. In: Curr Eye Res 34, 2009, pp. 360-268, PMID 19401879 .
D. Soewarto et al .: Features and strategies of ENU mouse mutagenesis. In: Curr Pharm Biotechnol 10, 2009, pp. 198-213, PMID 19199953 .
LB Russell LB and CS Montgomery: Supermutagenicity of ethylnitrosourea in the mouse spot test: comparisons with methylnitrosourea and ethylnitrosourethane. In: Mutat Res 92, 1982, pp. 193-204, PMID 7088002 .
SP Cordes: N-ethyl-N-nitrosourea mutagenesis: boarding the mouse mutant express. In: Microbiol Mol Biol Rev 69, 2005, pp. 426-439, PMID 16148305 .
B. Rathkolb et al .: Large-scale N-ethyl-N-nitrosourea mutagenesis of mice - from phenotypes to genes In: Exp Physiol 85, 2000, pp. 635-644, PMID 11187959 .
CL Kennedy and MK O'Bryan: N-ethyl-N-nitrosourea (ENU) mutagenesis and male fertility research. In: Hum Reprod Update 12, 2006, pp. 293-301, PMID 16436467 .
TV Tuyen Phenotypic and genotypic characterization of the ENU-induced mouse mutant HST001 for use in nephrological research. Dissertation, Ludwig Maximilians University Munich, 2005.

Web links

13th Report on Carcinogens (RoC): N-Nitroso-N-Ethylurea in Nitrosamines (PDF file; 940 kB)

[sigma-1] ta sheet N-Nitroso-N-ethylurea from Sigma-Aldrich , accessed on April 12, 2011 ( PDF ).

[2] C. Hansch et al: Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. American Chemical Society, 1995, p. 6.

[3] IARC ; Some Inorganic Substances, Chlorinated Hydrocarbons, Aromatic Amines, N-Nitroso Compounds and Natural Products. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans. 1972.

[4] IARC: Some N-Nitroso Compounds. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans. 1978.

[5] Entry on N-NITROSO-N-ETHYLUREA in the Hazardous Substances Data Bank , accessed on July 27, 2012.

[6] WL Russell et al .: Dose-response curve for ethylnitrosourea-induced specificlocus mutations in mouse spermatogonia. In: PNAS 79, 1982, pp. 3589-3591. PMID 6954505

[7] WL Russell et al .: Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. In: PNAS 76, 1979, pp. 5818-5819. PMID 293686

[8] C. Meyer: Phenotypic and metabolic physiological characterization of ENU (ethylnitrosourea) induced mouse mutants with impaired body weight regulation Dissertation, Philipps University Marburg, 2005.

[9] JK Noveroske include: The mutagenic action of N-ethyl-N-nitrosourea in the mouse. In: Mamm Genome 11, 2000, pp. 478-483, PMID 10886009 .

[10] EM Rinchik: Chemical mutagenesis and fine-structure functional analysis of the mouse genome. In: Trends Genet 7, 1991, pp. 15-21, PMID 2003334 .

[11] JS Weber et al.: Optimal N-ethyl-N-nitrosourea (ENU) doses for inbred mouse strains. In: Genesis 26, 2000, pp. 230-233, PMID 10748459 .