Disease relevance of N-Ethyl-N-nitrosourea

• Anchorage-independent growth of cells from the ethylnitrosourea-induced rat neuroblastoma line in which neu was originally detected by DNA transfection is also inhibited in the presence of anti-p185 monoclonal antibodies [1].
• Oxygens in DNA are main targets for ethylnitrosourea in normal and xeroderma pigmentosum fibroblasts and fetal rat brain cells [2].
• The neu oncogene is repeatedly activated in neuro- and glioblastomas derived by transplacental mutagenesis of the BDIX strain of rat with ethylnitrosourea [3].
• In a pedigree derived from a mouse treated with the mutagen ethylnitrosourea, a mutation has been identified that predisposes to spontaneous intestinal cancer [4].
• Opossums fed the chemical carcinogen ethyl nitrosourea early in postnatal life developed a variety of epithelial and mesenchymal embryonal neoplasms that were closely analogous, in morphology and biological behavior, to tumors of human infancy and childhood for which experimental models in laboratory animals are either imprecise or nonexistent [5].

Psychiatry related information on N-Ethyl-N-nitrosourea

• A small fraction of the animals develop B and T cell lymphomas after a long latency period, but the incidence is dramatically enhanced following administration of N-ethyl-N-nitrosourea, a carcinogen that induces DNA mutations [6].
• Using the alkaline filter elution technique we determined the induction and disappearance of DNA single-strand breaks (SSB) in freshly isolated peripheral blood lymphocytes (PBL) from 43 Alzheimer's disease (AD) patients and 48 normal, healthy age- and sex-matched control subjects following in vitro exposure to N-ethyl-N-nitrosourea (ENU) [7].

High impact information on N-Ethyl-N-nitrosourea

• Other mutations, induced by the random germ line mutagen ENU (N-ethyl-N-nitrosourea), have disclosed key molecules in the TLR signaling pathways and helped us to construct a reasonably sophisticated portrait of the afferent innate immune response [8].
• Here, we report the identification of a hyperactive N-ethyl-N-nitrosourea (ENU)-induced mouse mutant with abnormalities in the laminar architecture of the hippocampus and cortex, accompanied by impaired neuronal migration [9].
• ABL-1 does not antagonize germline apoptosis induced by the DNA-alkylating agent ethylnitrosourea [10].
• Conventional germ-cell mutagenesis with N-ethyl-N-nitrosourea (ENU) is compromised by an inability to monitor mutation efficiency, strain and interlocus variation in mutation induction, and extensive husbandry requirements [11].
• Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes [12].

Chemical compound and disease context of N-Ethyl-N-nitrosourea

• Inhibitory effect of phenobarbital on the development of gliomas in WF rats treated neonatally with N-ethyl-N-nitrosourea [13].
• Inbred CDF rats received 250 mg N-ethyl-N-nitrosourea (ENU)/kg body weight in monosodium phosphate buffer (pH 5.5) during late pregnancy (18-21 days) [14].
• Dideoxy chain-termination DNA sequencing was used to determine the specific DNA base changes induced after in vivo exposure of Escherichia coli to N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU) using the xanthine guanine phosphoribosyltransferase (gpt) gene as the genetic target [15].
• Treatment of adult female transgenic mice with N-ethyl-N-nitrosourea resulted in a dose-dependent increase of the frequency of mutated vectors isolated from brain DNA, up to 7.4 x 10(-5) at 250 mg of the alkylating agent per kilogram of body weight [16].
• In an N-ethyl-N-nitrosourea mutagenesis screen for recessive mutations we identified a mutant mouse with elevated concentrations of lysine, arginine and ornithine in urine, displaying the clinical syndrome of urolithiasis and its complications [17].

Biological context of N-Ethyl-N-nitrosourea

• Sensitivity to carcinogenesis in nude mice: skin tumors caused by transplacental exposure to ethylnitrosourea [18].
• The neu oncogene, identified in ethylnitrosourea-induced rat neuroglioblastomas, had strong homology with the erbB gene that encodes the epidermal growth factor receptor [19].
• In a search for genes that regulate circadian rhythms in mammals, the progeny of mice treated with N-ethyl-N-nitrosourea (ENU) were screened for circadian clock mutations [20].
• By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity [21].
• The N-Ethyl-N-Nitrosourea-induced germline mutation 3d (Unc3b1(3d/3d)) abolished both MHC class I and II responses elicited by this pathway, whereas a null allele of Cd36 selectively abolished class II responses [22].

Anatomical context of N-Ethyl-N-nitrosourea

• DNAs from nitrosoethylurea-induced rat neuroblastomas transform NIH/3T3 mouse fibroblasts in a transfection assay [23].
• Transplanted lymphomas, most of thymic origin, induced in BALB/c mice with 1-ethyl-1-nitrosourea (ENU) and transplanted spontaneously occurring lymphomas of AKR mice were examined for the expression of the T-cell antigens Ly, TL, and Thy 1 by using three serological methods [24].
• Analysis of an ethylnitrosourea-generated mouse mutation defines a cell intrinsic role of nuclear factor kappaB2 in regulating circulating B cell numbers [25].
• The chromosomes in 15 cell lines derived from separate tumors induced in rats by ethylnitrosourea (ENU) are described [26].
• Before transfer of the cells to culture, BD IX rat fetuses were treated with a single transplacental pulse of N-ethyl-N-nitrosourea (75 micrograms/g body wt) on the 18th day of gestation [27].

Associations of N-Ethyl-N-nitrosourea with other chemical compounds

• The present study was undertaken to evaluate the effect of phenobarbital (PB) on the development of neurogenic tumors induced in WF rats by neonatal administration of N-ethyl-N-nitrosourea (ENU; CAS: 759-73-9) [13].
• For the investigation of promoting effect, phenylbutazone was given as a dietary supplement for 2 years subsequent to initiation with N-ethyl-N-nitrosourea or N-propyl-N-nitrosourea [28].
• Six nitrosamides [ethylnitrosourea (ENU), 2-hydroxyethylnitrosourea (HENU), carboxymethylnitrosourea, 1-nitroso-5,6-dihydrouracil (NDHU), 1-nitrosohydantoin, and N-methyl-N-nitrosobenzamide (MNB)] and ethylnitrosocyanamide (ENC) were administered chronically in sodium citrate-buffered drinking water to MRC Wistar rats [29].
• Neurogenic tumors were selectively induced in high incidence in F344 rats by a single transplacental exposure to the direct-acting alkylating agent N-ethyl-N-nitrosourea (EtNU) [30].
• 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 [31].

Gene context of N-Ethyl-N-nitrosourea

• Here we report that two independent, postnatally lethal mutations induced by N-ethyl-N-nitrosourea and mapped near Tyr are alleles of Fah [32].
• Here, we describe a codominant CpG-ODN unresponsive phenotype that results from an N-ethyl-N-nitrosourea-induced missense mutation in the Tlr9 gene (Tlr9(CpG1)) [33].
• Here we report the identification of mutations in an extracellular matrix gene Fras1-related extracellular matrix gene 1 (Frem1) in both the classic head blebs mutant and in an N-ethyl-N-nitrosourea-induced allele [34].
• Rescue from embryonic lethality of mutant homozygotes (Eker/Eker) and suppression of N-ethyl-N-nitrosourea-induced renal carcinogenesis in heterozygotes (Eker/+) were both observed, defining the germ-line Tsc2 mutation in the Eker rat as embryonal lethal and tumor predisposing mutation [35].
• However, after treatment with the alkylating agent N-ethyl-N-nitrosourea, Aprt had a similar mutagenic response to Hprt while the majority (90%) of N-ethyl-N-nitrosourea-induced Aprt mutants had retained both alleles [36].

Analytical, diagnostic and therapeutic context of N-Ethyl-N-nitrosourea

• The cell lines were obtained by treating animals with a single transplacental dose of the carcinogen N-ethyl-N-nitrosourea (ENU) and 1) subsequently transferring brain cells into cell culture shortly after treatment or 2) explanting the resultant tumors from the offspring to monolayer cultures [37].
• Analysis of N-ethyl-N-nitrosourea-induced brain carcinogenesis by sequential culturing during the latent period. II. Morphology of the tumors induced by cell cultures [38].
• The surface microstructure of fetal rat brain cells undergoing neoplastic transformation in long-term cell culture after a single transplacental pulse of 75 microgram N-ethyl-N-nitrosourea/g body weight to the fetal (18th day of gestation) BD IX rat was investigated by scanning electron microscopy [39].
• Induction of duodenal tumors in F344 rats by continuous oral administration of N-ethyl-N-nitrosourea [40].
• N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: an animal model for human carbonic anhydrase II deficiency syndrome [41].

References