Ethylnitrosourea

ENU

Names
Systematic IUPAC name 1-Ethyl-1-nitrosourea
Other names N-Ethylnitrosourea N-Ethyl-N-nitrosourea Nitrosoethylurea
Identifiers
CAS Number	759-73-9 Y
3D model (Jmol)	Interactive image Interactive image
Abbreviations	ENU
Beilstein Reference	1761174
ChEBI	CHEBI:23995 Y
ChEMBL	ChEMBL167667 Y
ChemSpider	12427 Y
ECHA InfoCard	100.010.975
EC Number	212-072-2
KEGG	C19178 N
PubChem	12967
RTECS number	YT3150000
UN number	2811
InChI InChI=1S/C3H7N3O2/c1-2-6(5-8)3(4)7/h2H2,1H3,(H2,4,7) Y Key: FUSGACRLAFQQRL-UHFFFAOYSA-N Y
SMILES CCn(:n:[o]):c(:[nH2]):[o] CCN(N=O)C(N)=O
Properties
Chemical formula	C3H7N3O2
Molar mass	117.11 g·mol−1
log P	0.208
Acidity (pKa)	12.317
Basicity (pKb)	1.680
Hazards
GHS pictograms
GHS signal word	DANGER
GHS hazard statements	H301, H312, H332, H350, H360
GHS precautionary statements	P280, P308+313
EU classification (DSD)	T
R-phrases	R45, R46, R61, R20/21/22
S-phrases	S22, S36/37/39, S45
Lethal dose or concentration (LD, LC):
LD50 (median dose)	300 mg kg−1(oral, rat)
Related compounds
Related ureas	N-Nitroso-N-methylurea
Related compounds	N-Methylformamide Dimethylformamide Deuterated DMF Acetylleucine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N  (what is YN ?)
Infobox references

ENU, also known as N-ethyl-N-nitrosourea (chemical formula C₃H₇N₃O₂), is a highly potent mutagen. For a given gene in mice, ENU can induce 1 new mutation in every 700 loci. It is also toxic at high doses.

The chemical is an alkylating agent, and acts by transferring the ethyl group of ENU to nucleobases (usually thymine) in nucleic acids. Its main targets are the spermatogonial stem cells, from which mature sperm are derived.

Bill Russell (1951) created a landmark in the field of mouse genetics by creating a specifically designed mouse strain, the T (test) stock that was used in genetic screens for testing mutagens such as radiations and chemicals. The T-stock mouse harbors 7 recessive, viable mutations affecting easily recognizable traits. At the Oak Ridge National Laboratory, Russell's initial goal was to determine the rate of inheritable gene mutations in the germ line induced by radiations. Thus he decided to use T-stock mice in order to define how often a set of loci could be mutated with radiations. Since the mutations in the T-stock mouse were recessive, the progeny would have a wild type phenotype (as a result of crossing a mutant [e.g.s/s mutant male] to a wild type female [+/+]). Thus with any progeny carrying a mutation induced by radiation at one of the 7 loci, would exhibit the mutant phenotype in the first generation itself. This approach, the specific locus test (SLT) allowed Russell to study a wide range of specific mutations and to calculate the mutation rates induced by radiations.

In addition to studying the effect of radiation for SLT, Russell et al. were also interested in studying the effect of chemical mutagens such as procarbazine and ethylnitrosourea for SLT. At that time, procarbazine was the most potent chemical mutagen known to cause a significant spermatogonial mutagenesis in an SLT, although at a rate one-third of that of X-rays. Russell's earlier mutagenesis work on Drosophila using diethylnitrosoamine (DEN) triggered them to use DEN for the SLT. However, DEN needs to be enzymatically converted into an alkylating agent in order to be mutagenic and probably this enzymatic activation was not sufficient in mammals. This could be illustrated by the extremely low mutation rate in mice given by DEN (3 in 60,179 offsprings). To overcome this problem, a new mutagen, N-ethyl N-nitrosourea (ENU), an alkylating agent, which does not need to be metabolised, was suggested to be used by Ekkehart Vegel to Russell et al. The ENU (250 mg/kg) induced mice underwent a period of sterility for 10 weeks. After recovery, 90 males were crossed to the T-stock females and 7584 pups were obtained. Their results showed that a dose of 250 mg/kg of ENU was capable of producing a mutation rate 5 times higher than that obtained with 600R (1R = 2.6 x10^-4 coulombs/kg) of acute X-irradiation. This rate was also 15 times higher to that obtained with procarbazine (600 mg/kg).