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ethylnitrosourea

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Description

Ethylnitrosourea (ENU) is a potent alkylating agent that induces mutations in DNA. It is synthesized by reacting ethylurea with nitrous acid. ENU is an effective mutagen in a variety of organisms, including mice, rats, and zebrafish. Its ability to induce mutations in a wide range of genes makes it a valuable tool for generating animal models of human diseases. ENU is also used in forward genetic screens to identify genes involved in various biological processes. Studies have shown that ENU can induce point mutations, deletions, and insertions in DNA. These mutations can lead to a variety of phenotypic effects, including cancer, developmental defects, and neurological disorders. ENU is widely used in research to study the effects of genetic mutations and to identify genes involved in disease pathogenesis. Its importance lies in its ability to induce mutations in a specific and predictable manner, making it a powerful tool for understanding the genetic basis of disease.'

Ethylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

N-ethyl-N-nitrosourea : A member of the class of N-nitrosoureas that is urea in which one of the nitrogens is substituted by ethyl and nitroso groups. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID12967
CHEMBL ID167667
CHEBI ID23995
SCHEMBL ID77485
MeSH IDM0007914

Synonyms (67)

Synonym
unii-p8m1t4190r
1-ethyl-1-nitrosomocovina
p8m1t4190r ,
3-04-00-00233 (beilstein handbook reference)
aenh
ethylnitrosourea
ENU ,
n-nitroso-n-ethylurea
nitrosoethylurea
nsc 45403
n-ethyl-n-nitrosourea
n-ethylnitrosourea
1-ethyl-1-nitrosourea
urea, 1-ethyl-1-nitroso-
aethylnitroso-harnstoff
nsc-45403
nsc45403
wln: zvn2&no
759-73-9
urea, n-ethyl-n-nitroso-
NCGC00090828-01
n-ethyl-n-nitosourea
ccris 302
einecs 212-072-2
ethyl nitrosourea
hsdb 5111
n-ethyl-n-nitroso-urea
ne-urea
1-ethyl-1-nitrosomocovina [czech]
aethylnitroso-harnstoff [german]
n-ethyl-n-nitroso carbamide
aenh [german]
carbamide, n-ethyl-n-nitroso-
n-nitrosoethylurea
rcra waste no. u176
anh [german]
brn 1761174
rcra waste number u176
n-nitroso-n-ethylurea, isopac(r)
n-nitroso-n-ethylurea, bulk package
CHEBI:23995 ,
1-(aminocarbonyl)-1-ethyl-2-oxohydrazine
CHEMBL167667
NCGC00090828-02
AKOS006274354
C19178
dtxcid20593
dtxsid8020593 ,
NCGC00256468-01
tox21_302749
cas-759-73-9
tox21_202151
NCGC00259700-01
n-nitroso-n-ethyl urea, contains 40% water, 1.8 % acoh
FT-0607735
n-ethyl-n-nitrosourea [iarc]
n-ethyl-n-nitrosourea [mi]
n-nitroso-n-ethylurea [hsdb]
ethyl-1-nitrosourea, 1-
SCHEMBL77485
1-(aminocarbonyl)-1-ethyl-2-oxohydrazine #
FUSGACRLAFQQRL-UHFFFAOYSA-N
1-ethyl-1-nitroso-urea
Q287629
n-nitroso-n-ethyl urea, contains 40per cent water, 1.8 per cent acoh
EN300-206286
Z1198149309

Research Excerpts

Overview

Ethylnitrosourea (ENU) is a proven animal teratogen. It induced apoptosis and cell cycle arrest in the fetal central nervous system. The mechanism of its developmental toxicity is unknown.

ExcerptReferenceRelevance
"Ethylnitrosourea (ENU) is an alkylating agent and we previously clarified that it induced apoptosis and cell cycle arrest in the fetal central nervous system (CNS). "( Expression of p53 and its transcriptional target genes mRNAs in the ethylnitrosourea-induced apoptosis and cell cycle arrest in the fetal central nervous system.
Doi, K; Katayama, K; Nakayama, H; Ohtsuka, R; Takai, H, 2002
)
1.99
"Ethylnitrosourea (ENU) is a simple alkylating agent. "( Ethylnitrosourea-induced apoptosis in primordial germ cells of the rat fetus.
Doi, K; Katayama, K; Nakayama, H; Ueno, M; Yamauchi, H, 2002
)
3.2
"Ethylnitrosourea (ENU) is a proven animal teratogen, although the mechanism of its developmental toxicity is unknown. "( Chemically induced growth inhibition and cell cycle perturbations in cultures of differentiating rodent embryonic cells.
Faustman, EM; Ribeiro, PL, 1990
)
1.72
"Ethylnitrosourea is an alkylating reagent which preferentially modifies phosphates in nucleic acids. "( Probing the phosphates of the Escherichia coli ribosomal 16S RNA in its naked form, in the 30S subunit, and in the 70S ribosome.
Baudin, F; Ebel, JP; Ehresmann, B; Ehresmann, C; Eyermann, F; Mougel, M; Romby, P, 1989
)
1.72
"Ethylnitrosourea is an alkylating reagent preferentially modifying phosphate groups in nucleic acids. "( Yeast tRNAAsp tertiary structure in solution and areas of interaction of the tRNA with aspartyl-tRNA synthetase. A comparative study of the yeast phenylalanine system by phosphate alkylation experiments with ethylnitrosourea.
Bergdoll, M; Dumas, P; Ebel, JP; Giegé, R; Moras, D; Romby, P; Vlassov, VV; Westhof, E, 1985
)
1.9

Treatment

Mice treated with ethylnitrosourea (ENU) (45 mg/kg) on these gestation days developed a significantly increased tumour frequency in the lungs and liver, and in the ovaries.

ExcerptReferenceRelevance
"Treatment with ethylnitrosourea resulted in concentration-dependent, tissue-specific, and time-dependent mutation inductions consistent with known mechanisms of action."( Detection of mutations in transgenic fish carrying a bacteriophage lambda cII transgene target.
Brayer, KJ; Muller, SL; Norris, MB; Torres, C; Winn, RN, 2000
)
0.65
"Mice treated with ethylnitrosourea (ENU) (45 mg/kg) on these gestation days developed a significantly increased tumour frequency in the lungs and liver, and in the ovaries after treatment on day 15 of gestation."( Postnatal development and neoplastic disease pattern in NMRI mice after combined treatment with ethylnitrosourea and X-irradiation on different days of the fetal period.
Schmahl, W; Wiggenhauser, A, 1987
)
0.81

Toxicity

ExcerptReferenceRelevance
"We have examined the contributions of O6-alkylguanine-DNA alkyl-transferase (AGT) and nucleotide excision repair to the protection of human cells from the toxic and mutagenic effects of ethylnitrosourea."( Modulation of ethylnitrosourea-induced toxicity and mutagenicity in human cells by O6-benzylguanine.
Bronstein, SM; Hooth, MJ; Skopek, TR; Swenberg, JA, 1992
)
0.84
" We conclude that both AGT and NER play an important role in protecting human cells from the toxic and mutagenic effects of ENU."( Toxicity, mutagenicity, and mutational spectra of N-ethyl-N-nitrosourea in human cell lines with different DNA repair phenotypes.
Bronstein, SM; Cochrane, JE; Craft, TR; Skopek, TR; Swenberg, JA, 1991
)
0.28
" Qualitatively, the patterns of embryo malformations reported in treated embryos paralleled those observed in in vivo studies, especially in regard to adverse effects on central nervous system and craniofacial systems."( In vitro developmental toxicity of five direct-acting alkylating agents in rodent embryos: structure-activity patterns.
Faustman, EM; Gage, D; Kirby, Z; Varnum, M, 1989
)
0.28
" Corresponding analogues in Series A and B were equally toxic to HeLa-MR cells."( Aerobic and hypoxic toxicity of a new class of mixed-function drugs associating nitroimidazoles and chloroethylnitrosourea in nitrosourea-sensitive (Mer-) and -resistant (Mer+) human tumor cells.
Barascut, JL; Carminati, A; Imbach, JL; Mulcahy, RT, 1988
)
0.49
" Our observations lend support to the idea of a specific role for DNA adducts in defining MNU's toxic effects on cell viability and differentiation."( Modulation of nitrosourea toxicity in rodent embryonic cells by O6-benzylguanine, a depletor of O6-methylguanine-DNA methyltransferase.
Faustman, EM; Kidney, JK, 1995
)
0.29
" In methylcellulose cultures, ada-infected hematopoietic progenitor cells were twice as resistant as uninfected cells to the toxic effects of 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) following treatment with O6-BG."( Retroviral transfer of a bacterial alkyltransferase gene into murine bone marrow protects against chloroethylnitrosourea cytotoxicity.
Brent, TP; Edwards, CC; Harris, LC; Houghton, PJ; Marathi, UK; Sorrentino, BP; Srivastava, DK; Vanin, EF, 1995
)
0.51
" Three representative compounds, N-ethyl-N-nitrosourea (ENU), adriamycin (ADR), and mono-(2-ethylhexyl)phthalate (MEHP), toxic to different targets and known to affect germ cell development and impair fertility, were tested on PGCs in culture using three different experimental protocols."( A comparative study of cytotoxic effects of N-ethyl-N-nitrosourea, adriamycin, and mono-(2-ethylhexyl)phthalate on mouse primordial germ cells.
Ciccalese, R; De Felici, M; Iona, S; Klinger, FG; Nunziata, A; Sisti, R, 2002
)
0.31
" An attempt has been made in our lab to study the effect of nitrosocompound mediated toxicity and the gradual toxic effects of these neurotoxic agents to transform the normal glial cells to a neoplastic one."( Immunotherapeutic effects of T11TS/S-LFA3 against nitrosocompound mediated neural genotoxicity.
Chaudhuri, S; Duttagupta, AK; Ghosh, A; Mukherjee, J; Sarkar, S, 2004
)
0.32
" This metalloid acts as a promoter of carcinogenesis, exerting toxic effects on the immune system."( Immunological profile of arsenic toxicity: a hint towards arsenic-induced carcinogenesis.
Acharya, S; Begum, Z; Chatterjee, S; Chaudhuri, S; Dasgupta, S; Flora, SJ; Kumar, P, 2010
)
0.36
" The present study was performed to investigate the toxic effects of a suggested ENU treatment protocol (100 mg/kg ENU once a week for three consecutive weeks) on the C57BL/6J mouse testis using light and transmission electron microscopy, with reference to testis weight and sperm count."( Time-dependent toxic effects of N-ethyl-N-nitrosourea on the testes of male C57BL/6J mice: a histological and ultrastructural study.
Chen, B; Sun, K; Yin, J, 2015
)
0.42

Pharmacokinetics

ExcerptReferenceRelevance
" These results suggested that the superior activity of CNC-alanylalanine over CNC-glycinemethylamide against MAC 15A in vivo could be attributed mainly to differences in the pharmacokinetic behaviour of the two drugs following intraperitoneal administration and that CNC-alanylalanine might have a role in the treatment of local peritoneal disease."( Pharmacokinetic studies of chloroethylnitrosocarbamoyl-amino acid derivatives in vivo and in vitro.
Bibby, MC; Eisenbrand, G; Matthew, AM,
)
0.13

Compound-Compound Interactions

ExcerptReferenceRelevance
" At this time of gestation, developmental anomalies of the brain are still inducible by any of these treatments, in addition to neurocarcinogenic effects after ENU alone or in combination with X-irradiation."( Correlations between the degree and type of forebrain malformations and the simultaneous neuro-oncogenic properties of ethylnitrosourea after diaplacental exposure in rats, alone and in combination with X-irradiation.
Kriegel, H; Schmahl, W, 1985
)
0.48
"The purpose of this study was to further evaluate the therapeutic efficacy of convection enhanced delivery (CED) of carboplatin in combination with radiotherapy for treatment of the F98 rat glioma."( Convection enhanced delivery of carboplatin in combination with radiotherapy for the treatment of brain tumors.
Barth, RF; Chou, TC; Elleaume, H; Grecula, JC; Gupta, N; Hoff, BA; Huo, T; Ross, BD; Rousseau, J; Weldon, M; Yang, W, 2011
)
0.37

Bioavailability

ExcerptReferenceRelevance
" Transformation may be impeded by a low rate of absorption of carcinogenic agents (barrier effect), by the availability of deactivating enzymes operative at several steps of the metabolism of carcinogenic agents, and by a high repair capability of DNA damage."( Potential factors in carcinogenesis and tumor regression.
Koestner, A, 1983
)
0.27

Dosage Studied

A dose-response analysis was carried out with 2 independent data sets available for ethylnitrosourea-induced specific-locus mutations in spermatogonia of the mouse. The mutation frequency induced by a 400 mg/kg dosage is 12 times the maximal mutation frequency achievable with a single exposure to x-rays.

ExcerptRelevanceReference
"The results of transplacental induction of brain tumours by a single intravenous injection of ethylnitrosourea in a dosage of 20 or 30 mg/kg body weight to pregnant BD IX and Albino rats on the 17th day of gestation are presented."( [Early stages of experimental brain tumours in rats. Investigation of serial sections (author's transl)].
Gerlach, H; Peschel, B; Rath, FW; Schreiber, D; Wessel, H, 1978
)
0.48
" These predictions were in reasonably good agreement with the observed dose-response data for these agents."( Alkylation of deoxyribonucleic acid in vivo in various organs of C57BL mice by the carcinogens N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea and ethyl methanesulphonate in relation to induction of thymic lymphoma. Some applications of high-pressure liquid
Frei, JV; Lawley, PD; Swenson, DH; Warren, W, 1978
)
0.26
" The dose was determined in a prior dose-response investigation."( A preliminary investigation of promotion of brain tumours by hexachlorophane in Sprague-Dawley rats transplacentally exposed to N-ethylnitrosourea.
Dayan, A; Purves, D, 1992
)
0.49
"The variant frequencies for 6-thioguanine-resistant spleen cells in different mouse strains have been estimated by autoradiography for animals without chemical treatment and in cases of in vivo mutagen dosage with ethylnitrosourea and cyclophosphamide, respectively."( Detection of 6-thioguanine-resistant spleen lymphocytes in different mouse strains by autoradiography.
Braun, R; Hüttner, E; Schöneich, J; Wielgosz, SM, 1991
)
0.47
" To determine the importance in germ-line mutagenesis of the O6-G site relative to the N-7 of guanine, dose-response curves were constructed for both ENU and EMS, where dose was measured as total adducts per deoxynucleotide (APdN) and response as sex-linked recessive lethals (SLRL) induced in Drosophila melanogaster spermatozoa."( Comparison of dose-response relationships for ethyl methanesulfonate and 1-ethyl-1-nitrosourea in Drosophila melanogaster spermatozoa.
Beranek, DT; Byrne, BJ; Lee, WR; Tucker, AB, 1990
)
0.28
" There was no linearity in the dose-response relationship at the lower dose (50 micrograms/g), as was the case with the specific-locus mutation."( An examination of respiratory distress and chromosomal abnormalities in the offspring of male mice treated with ethylnitrosourea.
Gotoh, H; Namba, T; Nomura, T, 1990
)
0.49
"A dose-response analysis was carried out with 2 independent data sets available for ethylnitrosourea-induced specific-locus mutations in spermatogonia of the mouse."( A dose-response analysis of ethylnitrosourea-induced recessive specific-locus mutations in treated spermatogonia of the mouse.
Ehling, UH; Favor, J; Neuhäuser-Klaus, A; Sund, M, 1990
)
0.8
" For both compounds, very similar dose-response curves were found for induction of chromatid breaks in the dose range 10-75 mg/kg."( Transplacental genetic and cytogenetic effects of alkylating agents in the mouse. II. Induction of chromosomal aberrations.
Braun, R; Hüttner, E; Schöneich, J, 1986
)
0.27
" with one 25 mg/kg dose of dimethylnitrosamine (DMN) as neonates or dosed twice orally with 7,12-dimethylbenz[a]anthracene (DMBA) shortly after ovariectomy."( Differential renal tumor response to N-ethylnitrosourea and dimethylnitrosamine in the Nb rat: basis for a new rodent model of nephroblastoma.
Hard, GC, 1985
)
0.54
" The dose-response for the induction of mutations in the plasmid-encoded gene closely paralleled that for the induction of mutations in the cellular gene for hypoxanthine (guanine) phosphoribosyltransferase."( Chemically induced mutagenesis in a shuttle vector with a low-background mutant frequency.
Drinkwater, NR; Klinedinst, DK, 1986
)
0.27
" For treatments resulting in fewer than 2 lethal hits, MNU, ENU, and MC gave rise to apparently linear dose-response curves for gene mutations (hgprt and tk genes) as well as for chromosomal aberrations."( Spontaneous and induced chromosomal aberrations and gene mutations in human lymphoblasts: mitomycin C, methylnitrosourea, and ethylnitrosourea.
Jensen, JC; Thilly, WG, 1986
)
0.49
" MMS and ENU both showed shouldered dose-response curves for exponentially growing asynchronous cells, and the same cell-cycle pattern for synchronous cultures with cells in early S phase being the most sensitive."( Cell killing by various monofunctional alkylating agents in Chinese hamster ovary cells.
Goth-Goldstein, R; Hughes, M, 1987
)
0.27
" Due to unequal variances of the number of SCEs in the various treatment groups, a weighted least-squares analysis was used to estimate the parameters of the dose-response relationship."( Evaluation of the interaction of three genotoxic agents in eliciting sister-chromatid exchanges using response surface methodology.
Carchman, RA; Carter, WH; Chinchilli, VM; Solana, RP; Wilson, JD, 1987
)
0.27
"To investigate the hypothesis that the similarity of dose-response curves for induction of thymic lymphoma in C57BL mice was due to similar DNA alkylation profiles for 1-ethyl-1-nitrosourea (ENU) and 1-(2-hydroxyethyl)-1-nitrosourea (HNU), we measured the reaction of the two agents with DNA in vitro and in target tissues in vivo."( The binding of 1-(2-hydroxyethyl)-1-nitrosourea to DNA in vitro and to DNA of thymus and marrow in C57BL mice in vivo.
Harbach, PR; Petzold, GL; Swenson, DH, 1986
)
0.27
" The dose-response curve was found to be linear."( Linear dose-response relationship of erythrocyte enzyme-activity mutations in offspring of ethylnitrosourea-treated mice.
Charles, DJ; Pretsch, W, 1987
)
0.49
" The mutation frequency induced by a 400 mg/kg dosage of ethylnitrosourea is 12 times the maximal mutation frequency achievable with a single exposure to x-rays and 36 times that reported for procarbazine, the most effective chemical mutagen previously known for mouse stem-cell spermatogonia."( Dose-repetition increases the mutagenic effectiveness of N-ethyl-N-nitrosourea in mouse spermatogonia.
Carpenter, DA; Hitotsumachi, S; Russell, WL, 1985
)
0.51
"Carcinogenic risk assessment of chemicals consists of four phases, namely, 1) hazard identification, 2) exposure assessment, 3) hazard assessment or dose-response assessment, and 4) risk characterization."( Risk evaluation of tumor-inducing substances in foods.
Hayashi, Y; Kurokawa, Y; Maekawa, A, 1985
)
0.27
" Two-parameter (DNA, RNA) flow cytometry measurements showed a dose-response relationship in the loss of certain cell types, particularly the elongated spermatids, from the testes of treated animals."( Flow cytometric analysis of mouse spermatogenic function following exposure to ethylnitrosourea.
Ballachey, BE; Evenson, DP; Grueneberg, D; Higgins, PJ, 1985
)
0.5
" In general, a dose-response effect was evident in the number and magnitude of neurochemical alterations produced by ENU."( Nucleic acids and protein in brains and cerebella of rats transplacentally exposed to ethylnitrosourea.
McLaughlin, PJ; Zagon, IS, 1981
)
0.49
" A comparison of the histological structure and histochemical properties of malignant tumors showed their being independent on the chemical structure, dosage and terms of the carcinogen administration."( [Enzymohistochemical study of the tumors from the transplacental and postnatal exposure to various carcinogens].
Kolodin, VI; P''rvanova, LG, 1980
)
0.26
" The dose-response relationship for induction of reverse mutations by ENU appears not to deviate from linearity."( Establishment of a dose-response relationship for reverse mutation at the HPRT (hypoxanthine guanine phosphoribosyl transferase) locus L5178Y mouse lymphoma cells.
Knaap, AG; Meera Khan, P; Simons, JW, 1982
)
0.26
"The shape of the dose-response curve for mutations induced at low doses of mutagenic agents in mammalian cells was studied."( Relationship between chemical damage of DNA and mutations in mammalian cells. I. Dose-response curves for the induction of 6-thioguanine-resistant mutants by low doses of monofunctional alkylating agents, X-rays and UV radiation in V79 Chinese hamster cel
Jenssen, D; Ramel, C, 1980
)
0.26
" In view of the current interest in the provitamin as a cancer chemopreventive agent, and the association between mutagenesis and carcinogenesis, we have dosed Fischer 344 rats with model carcinogen N-ethyl-N-nitrosourea (ENU) and investigated the relationships among BC intake, its tissue accumulation, and antimutagen activity."( In vivo antimutagenic activity of beta-carotene in rat spleen lymphocytes.
Aidoo, A; Bishop, ME; Lensing, S; Lyn-Cook, LE; Wamer, W, 1995
)
0.29
" Dose-response studies with the lambda lacZ mice indicated a threshold for mutation induction in stem cells at low ENU dosages, which is in accordance with the specific-locus test data."( Germ cell mutagenesis in lambda lacZ transgenic mice treated with ethylnitrosourea; comparison with specific-locus test.
Baan, RA; van Delft, JH, 1995
)
0.53
" Although a few of the 50 mg/kg split-dose treatments were significantly higher than the comparative single-dose groups, the number of TGr lymphocytes produced by the two dosing regimens were generally similar."( The effect of time after treatment, treatment schedule and animal age on the frequency of 6-thioguanine-resistant T-lymphocytes induced in Fischer 344 rats by N-ethyl-N-nitrosourea.
Aidoo, A; Casciano, DA; George, EO; Heflich, RH; Lyn-Cook, LE, 1993
)
0.29
" Several studies have shown that RB dosage is important in determining biological effects."( Susceptibility to tumors induced in mice by ethylnitrosourea is independent of retinoblastoma gene dosage.
Chang, CY; Jones, D; Lai, CC; Lee, EY; Lee, WH; Riley, DJ, 1994
)
0.55
" In this study, we have investigated the antimutagenic effects of ascorbic acid on the frequency of 6-thioguanine-resistant (6-TGr) T-lymphocytes produced in Fischer 344 rats dosed with the direct-acting alkylating agent, N-ethyl-N-nitrosourea (ENU)."( Ascorbic acid (vitamin C) modulates the mutagenic effects produced by an alkylating agent in vivo.
Aidoo, A; Lensing, S; Lyn-Cook, LE; Wamer, W, 1994
)
0.29
" We previously reported that ionizing radiation induces additional tumors in a linear dose-response relationship, suggesting that in heterozygotes two events (one inherited, one somatic) are necessary to produce tumors."( Allelic loss at the predisposing gene locus in spontaneous and chemically induced renal cell carcinomas in the Eker rat.
Hino, O; Kubo, Y; Mitani, H, 1994
)
0.29
" ENU dose-response curves were similar."( Comparison of somatic mutation in a transgenic versus host locus.
Heddle, JA; Tao, KS; Urlando, C, 1993
)
0.29
" The suppressive action of the wild-type gene over its mutationally activated oncogenic homologue underlines the critical function of the neu gene in the control of differentiation in the Schwann cell lineage, and provides evidence for the responsiveness of cellular phenotypes towards quantitative shifts in the dosage of wild-type vs mutant signal transducing molecules."( Wild type neu transgene counteracts mutant homologue in malignant transformation of rat Schwann cells.
Flesken-Nikitin, A; Jin, JJ; Nikitin, AY; Papewalis, J; Pozharisski, KM; Prokopenko, SN; Rajewsky, MF; Winterhager, E, 1996
)
0.29
"5 PGC, and multiple dosing of 25 mg/kg ENU showed an additive effect."( Dose-dependent induction of recessive mutations with N-ethyl-N-nitrosourea in primordial germ cells of male mice.
Hara, T; Horiya, N; Matsuda, H; Sakamoto, K; Shibuya, T, 1996
)
0.29
" Although the initial level of a specific alkylation product (O6-ethylguanine) in nuclear DNA was uniform, different dose-response curves were obtained for the comet size in individual cell samples immediately after exposure, with small intercellular variation."( DNA excision repair profiles of normal and leukemic human lymphocytes: functional analysis at the single-cell level.
Buschfort, C; Muller, MR; Rajewsky, MF; Seeber, S; Thomale, J, 1997
)
0.3
" The lacI mutant frequencies were significantly elevated in transgenic mice dosed with ENU at 150 mg/kg (2-fold increase above control) and iPMS at 200 mg/kg (3-fold increase above control) but not in those receiving MMS at 40 mg/kg."( Evaluation of spontaneous and chemical-induced lacI mutations in germ cells from lambda/lacI transgenic mice.
Carr, GJ; Putman, DL; Ritter, AP; Young, RR, 1997
)
0.3
" The critical steps of the assay, however, seem to be dosing and sampling time."( Detection of the two germ cell mutagens ENU and iPMS using the LacZ/transgenic mouse mutation assay.
Liegibel, UM; Schmezer, P, 1997
)
0.3
" Similar dose-response curves were measured for the three polymerases examined; thus the identity of the DNA polymerase does not appear to affect the mutagenic potency of ethyl lesions."( Development and use of an in vitro HSV-tk forward mutation assay to study eukaryotic DNA polymerase processing of DNA alkyl lesions.
Eckert, KA; Hile, SE; Vargo, PL, 1997
)
0.3
"Our earlier analyses have suggested an apparent threshold dose-response for ethylnitrosourea-induced specific-locus mutations in treated spermatogonia of the mouse to be due to a saturable repair process."( The effect of the interval between dose applications on the observed specific-locus mutation rate in the mouse following fractionated treatments of spermatogonia with ethylnitrosourea.
Ehling, UH; Favor, J; Neuhäuser-Klaus, A; van Zeeland, AA; Wulff, A, 1997
)
0.72
"The dose-response relation for the appearance of pepsinogen isozyme 1 (Pg 1)-altered pyloric glands (PAPG) and the related induction of adenocarcinomas were examined in male C3H mice given N-methyl-N-nitrosourea (MNU) in their drinking water at the concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group 3) or 0 ppm (group 4) for 30 weeks and then normal tap water."( Dose-dependent induction of both pepsinogen-altered pyloric glands and adenocarcinomas in the glandular stomach of C3H mice treated with N-methyl-N-nitrosourea.
Fujimitsu, Y; Furihata, C; Imai, T; Inada, K; Nakanishi, H; Tatematsu, M; Yamamoto, M, 1997
)
0.3
" In the small intestine, treatment with various dosages of ENU (10-150 mg/kg) resulted in a linear dose-response in both lacZ and Dlb-I."( Gene-mutation assays in lambda lacZ transgenic mice: comparison of lacZ with endogenous genes in splenocytes and small intestinal epithelium.
Baan, RA; Bergmans, A; Howard, L; Tates, AD; van Dam, FJ; van Delft, JH; Winton, DJ, 1998
)
0.3
" We describe (i) an efficient recombinant approach to produce PAL enzyme, (ii) testing of PAL in orthologous N-ethyl-N'-nitrosourea (ENU) mutant mouse strains with HPA, and (iii) proofs of principle (PAL reduces HPA)-both pharmacologic (with a clear dose-response effect vs."( A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase.
Blain, F; Chang, TM; Heft, R; Peevers, R; Sarkissian, CN; Scriver, CR; Shao, Z; Su, H, 1999
)
0.3
" To perform an effective ENU mutagenesis screen using inbred mice, a dosage regimen is required to determine the optimal dose of ENU for that inbred strain, a time-consuming preliminary process."( Optimal N-ethyl-N-nitrosourea (ENU) doses for inbred mouse strains.
Justice, MJ; Salinger, A; Weber, JS, 2000
)
0.31
" ENU dosage (4 mg/kg) was selected to give an expected brain tumor incidence of 10-15% over the mean life span of 26 months."( Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats exposed to frequency-modulated microwave fields.
Adey, WR; Byus, CV; Cain, CD; Higgins, RJ; Jones, RA; Kean, CJ; Kuster, N; MacMurray, A; Stagg, RB; Zimmerman, G, 2000
)
0.31
"With dosage increased, survival rate of plated cell reduced (in the group with dosage of ENU with 100-200 micro g/ml, P<0."( Analysis of spontaneous, gamma ray- and ethylnitrosourea-induced hprt mutants in HL-60 cells with multiplex PCR.
An, H; Cao, J; Liu, SX; Liu, Y; Shun, HM; Yang, LJ, 2003
)
0.59
" In dose-response experiments trend of decreasing amount of DNA synthesis was observed, but no statistical differences were found."( The effects of mono-2-ethylhexyl phathalate, adriamycin and N-ethyl-N-nitrosourea on stage-specific apoptosis and DNA synthesis in the mouse spermatogenesis.
Hakovirta, H; Linderborg, J; Nikula, H; Parvinen, M; Suominen, JS; Toppari, J, 2003
)
0.32
" ENU also induces genetic lesions in somatic cells and dosage requires optimization between maximum germline mutation rate versus induced sterility and tumourigenesis that compromise the welfare and fecundity of the ENU-treated males."( Analysis of breeding and pathology helps refine management practices of a large-scale N'-ethyl-N'-nitrosourea mouse mutagenesis programme.
Cheeseman, MT; Dear, N; Humphreys, J; Polley, S; Smith, AP; Stewart, M; Vizor, L; Warren, MV; Wells, S, 2009
)
0.35
" Carcinogenic susceptibility is therefore consistent with the involvement of one major autosomal locus; the operation of a gene dosage effect; and a lack of simple Mendelian dominance for either susceptibility or resistance."( Inheritance of susceptibility to induction of nephroblastomas in the Noble rat.
Diwan, BA; Fortini, ME; Perantoni, AO; Rice, JM; Sharma, N; Timofeeva, O; Wang, H; Yang, Y, 2009
)
0.35
" Doses up to 80mg/kg/day (7-day dosing regime) did not induce micronuclei in mouse bone marrow."( MNT and MutaMouse studies to define the in vivo dose response relations of the genotoxicity of EMS and ENU.
Ballantyne, M; Gocke, E; Müller, L; Whitwell, J, 2009
)
0.35
" In this study, we examined the accumulation and persistence of Pig-A mutant RBCs in rats treated with N-ethyl-N-nitrosourea (ENU) using two dosing schedules."( Accumulation and persistence of Pig-A mutant peripheral red blood cells following treatment of rats with single and split doses of N-ethyl-N-nitrosourea.
Dobrovolsky, VN; Heflich, RH; Kasahara, Y; Kimoto, T; Miura, D,
)
0.13
" Moreover, older mice (25 to 34 weeks of age) received the same dosage and were sacrificed 7 days later."( Corneal damage induced in adult mice by a single intraperitoneal injection of N-ethyl-N-nitrosourea.
Kimura, A; Kuro, M; Miki, H; Sasaki, T; Tsubura, A; Uehara, N; Yoshizawa, K; Yuri, T,
)
0.13
"In recent years, experimental evidence has accumulated that supports the existence of sublinear dose-response relationships at low doses of DNA reactive mutagens."( Defining EMS and ENU dose-response relationships using the Pig-a mutation assay in rats.
Cammerer, Z; Coffing, SL; Dobo, KL; Fiedler, RD; Gunther, WC; Schuler, M; Shutsky, T; Thiffeault, CJ, 2011
)
0.37
" Additionally, it is quite common to have high levels of mortality in any particular dosing cycle."( Enhancing the efficiency of N-ethyl-N-nitrosourea-induced mutagenesis in the zebrafish.
Frohnhöfer, HG; Harris, MP; Perathoner, S; Rohner, N, 2011
)
0.37
" In this study, we investigated the effect of dosing time on micronucleus induction in the bone marrow by evaluating the frequencies of micronucleated peripheral reticulocytes (MNRETs) in mice exposed to N-ethyl-N-nitrosourea (ENU) to assess any difference in genotoxic sensitivity to chemicals between light and dark periods (inactive phase for rodents and active phase for rodents)."( Differences in micronucleus induction in peripheral blood reticulocytes of mice exposed to N-ethyl-N-nitrosourea at light and dark dosing times.
Hayashi, M; Itoh, K; Masumori, S; Nakajima, M; Sakakibara, H; Shimoi, K, 2012
)
0.38
" As a continuation of our earlier report that analyzed ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS) dose-response data (Gollapudi et al."( Derivation of point of departure (PoD) estimates in genetic toxicology studies and their potential applications in risk assessment.
Abraham, L; Bodger, OG; Dearfield, KL; Gollapudi, BB; Heflich, RH; Hixon, JG; Johnson, GE; Lovell, DP; MacGregor, JT; Pottenger, LH; Soeteman-Hernández, LG; Tanir, JY; Thompson, CM; Thybaud, V; van Benthem, J; White, PA; Zeiger, E, 2014
)
0.4
"The transgenic rodent mutation assay was used to compare the dose-response relationship of lacZ mutant frequency (MF) in spermatogonial stem cells exposed acutely or subchronically to N-ethyl-N-nitrosourea (ENU)."( Sublinear response in lacZ mutant frequency of Muta™ Mouse spermatogonial stem cells after low dose subchronic exposure to N-ethyl-N-nitrosourea.
Douglas, GR; Marchetti, F; O'Brien, JM; Sivathayalan, A; Walker, M; Yauk, CL, 2015
)
0.42
" In this study, two lower doses (10 and 30mg/kg) were added, and dose-response of inherited germline mutations was analyzed."( Dose-dependent de novo germline mutations detected by whole-exome sequencing in progeny of ENU-treated male gpt delta mice.
Gondo, Y; Honma, M; Masumura, K; Nohmi, T; Toyoda-Hokaiwado, N; Ukai, A, 2016
)
0.43
" This ENU dosing regimen also increased the frequency of CD59-negative erythrocytes."( Applying the erythrocyte Pig-a assay concept to rat epididymal sperm for germ cell mutagenicity evaluation.
Ji, Z; LeBaron, MJ, 2017
)
0.46
"There is growing interest in quantitative analysis of in vivo genetic toxicity dose-response data, and use of point-of-departure (PoD) metrics such as the benchmark dose (BMD) for human health risk assessment (HHRA)."( Comparing BMD-derived genotoxic potency estimations across variants of the transgenic rodent gene mutation assay.
Battaion, HL; Johnson, GE; Slob, W; White, PA; Wills, JW, 2017
)
0.46
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (4)

RoleDescription
alkylating agentHighly reactive chemical that introduces alkyl radicals into biologically active molecules and thereby prevents their proper functioning. It could be used as an antineoplastic agent, but it might be very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. It could also be used as a component of poison gases.
mutagenAn agent that increases the frequency of mutations above the normal background level, usually by interacting directly with DNA and causing it damage, including base substitution.
carcinogenic agentA role played by a chemical compound which is known to induce a process of carcinogenesis by corrupting normal cellular pathways, leading to the acquistion of tumoral capabilities.
genotoxinA role played by a chemical compound to induce direct or indirect DNA damage. Such damage can potentially lead to the formation of a malignant tumour, but DNA damage does not lead inevitably to the creation of cancerous cells.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
N-nitrosoureasA nitroso compound that is any urea in which one of the nitrogens is substituted by a nitroso group
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (10)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
interleukin 8Homo sapiens (human)Potency37.57800.047349.480674.9780AID651758
pregnane X receptorRattus norvegicus (Norway rat)Potency35.48130.025127.9203501.1870AID651751
GLI family zinc finger 3Homo sapiens (human)Potency67.26650.000714.592883.7951AID1259369
progesterone receptorHomo sapiens (human)Potency26.77930.000417.946075.1148AID1346784
glucocorticoid receptor [Homo sapiens]Homo sapiens (human)Potency12.56320.000214.376460.0339AID720692
retinoic acid nuclear receptor alpha variant 1Homo sapiens (human)Potency38.31050.003041.611522,387.1992AID1159552; AID1159555
estrogen nuclear receptor alphaHomo sapiens (human)Potency19.91140.000229.305416,493.5996AID743069
activating transcription factor 6Homo sapiens (human)Potency0.70650.143427.612159.8106AID1159516
nuclear factor erythroid 2-related factor 2 isoform 1Homo sapiens (human)Potency74.97800.000627.21521,122.0200AID651741
lethal factor (plasmid)Bacillus anthracis str. A2012Potency31.62280.020010.786931.6228AID912
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (1)

Assay IDTitleYearJournalArticle
AID227561Compound was evaluated for its ability to exhibit alkylating property toward DNA at 5 mM in 180 min1980Journal of medicinal chemistry, Jul, Volume: 23, Issue:7
Noval antitumor nitrosoureas and related compounds and their reactions with DNA.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (2,254)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990812 (36.02)18.7374
1990's530 (23.51)18.2507
2000's545 (24.18)29.6817
2010's334 (14.82)24.3611
2020's33 (1.46)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 22.36

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index22.36 (24.57)
Research Supply Index7.77 (2.92)
Research Growth Index4.34 (4.65)
Search Engine Demand Index31.58 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (22.36)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (0.04%)5.53%
Reviews132 (5.56%)6.00%
Case Studies6 (0.25%)4.05%
Observational0 (0.00%)0.25%
Other2,237 (94.15%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]