Genomes and Genes
Summary: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.
- Tronov V, Loginova M, Kramarenko I. [Methylnitrosourea as challenge mutagen in assessment of the DNA mismatch repair (MMR) activity: association with some types of cancer]. Genetika. 2008;44:686-92 pubmed..The present study was focused on analysis of the effect of methylnitrosourea (MNU) on resting and PHA-stimulated lymphocytes from healthy donors and patients with gynecological cancer...
- Hoivik D, Allen J, Wall H, Nold J, Miller R, Santostefano M. Studies evaluating the utility of N-methyl-N-nitrosourea as a positive control in carcinogenicity studies in the p53+/- mouse. Int J Toxicol. 2005;24:349-56 pubmed..The increased incidence of neoplastic and proliferative changes in MNU-treated mice suggests MNU could serve as a positive control in alternative carcinogenicity studies conducted in p53+/- knockout mice. ..
- Lubet R, Christov K, Nunez N, Hursting S, Steele V, Juliana M, et al. Efficacy of Targretin on methylnitrosourea-induced mammary cancers: prevention and therapy dose-response curves and effects on proliferation and apoptosis. Carcinogenesis. 2005;26:441-8 pubmed..and chemotherapeutic properties of the RXR receptor agonist Targretin (LGD 1069) were examined in the methylnitrosourea (MNU)-induced model of mammary cancer. The administration of Targretin at dose levels of 60, 20 or 6...
- Thompson H, Singh M. Rat models of premalignant breast disease. J Mammary Gland Biol Neoplasia. 2000;5:409-20 pubmed..Opportunities to investigate the biological and molecular characteristics of premalignant breast disease in the rat are presented. ..
- Petrin D, Baker A, Coupland S, Liston P, Narang M, Damji K, et al. Structural and functional protection of photoreceptors from MNU-induced retinal degeneration by the X-linked inhibitor of apoptosis. Invest Ophthalmol Vis Sci. 2003;44:2757-63 pubmed..The results suggest that XIAP is protective against this potent chemotoxic agent and holds promise as a therapeutic agent in gene therapy approaches to treating retinitis pigmentosa. ..
- Yoshizawa K, Tsubura A. [Characteristics of N-methyl-N-nitrosourea-induced retinal degeneration in animals and application for the therapy of human retinitis pigmentosa]. Nippon Ganka Gakkai Zasshi. 2005;109:327-37 pubmed..Thus, suppression of MNU-induced photoreceptor cell apoptosis in animals may provide therapeutic information for RP control in humans. ..
- Till B, Cooper J, Tai T, Colowit P, Greene E, Henikoff S, et al. Discovery of chemically induced mutations in rice by TILLING. BMC Plant Biol. 2007;7:19 pubmed..By comparison to other plants used in public TILLING services, we conclude that the populations described here would be suitable for use in a large scale TILLING project. ..
- Rajkumar L, Guzman R, Yang J, Thordarson G, Talamantes F, Nandi S. Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments. Breast Cancer Res. 2004;6:R31-7 pubmed..The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations. ..
- Smits B, Sharma D, Samuelson D, Woditschka S, Mau B, Haag J, et al. The non-protein coding breast cancer susceptibility locus Mcs5a acts in a non-mammary cell-autonomous fashion through the immune system and modulates T-cell homeostasis and functions. Breast Cancer Res. 2011;13:R81 pubmed publisher..The resistant Mcs5a allele is associated with alterations in T-cell homeostasis and functions, and overabundance of ??TCR+ T-cells in carcinogen-exposed mammary epithelium. ..
- Leung W, Wu K, Wong C, Cheng A, Ching A, Chan A, et al. Transgenic cyclooxygenase-2 expression and high salt enhanced susceptibility to chemical-induced gastric cancer development in mice. Carcinogenesis. 2008;29:1648-54 pubmed publisher..In conclusion, both high salt and COX-2 overexpression promote chemical-induced gastric carcinogenesis, possibly related to chronic inflammation, induction of PGE(2), disruption of cell kinetics and induction of inflammatory cytokines. ..
- Grubbs C, Hill D, Bland K, Beenken S, Lin T, Eto I, et al. 9cUAB30, an RXR specific retinoid, and/or tamoxifen in the prevention of methylnitrosourea-induced mammary cancers. Cancer Lett. 2003;201:17-24 pubmed..When suboptimal doses of 9cUAB30 were given in the methylnitrosourea (MNU)-induced mammary cancer model, the following average number of mammary cancers were observed: 9cUAB30 (..
- Miki K, Uehara N, Shikata N, Matsumura M, Tsubura A. Poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide rescues N-methyl-N-nitrosourea-induced photoreceptor cell apoptosis in Sprague-Dawley rats through preservation of nuclear factor-kappaB activity. Exp Eye Res. 2007;84:285-92 pubmed..Thus, 3-AB dose-dependently suppressed MNU-induced retinal damage, and 50mg/kg 3-AB injected concurrently with MNU completely rescued photoreceptor cell apoptosis via preservation of NF-kappaB activity. ..
- Durando M, Kass L, Piva J, Sonnenschein C, Soto A, Luque E, et al. Prenatal bisphenol A exposure induces preneoplastic lesions in the mammary gland in Wistar rats. Environ Health Perspect. 2007;115:80-6 pubmed..Our results demonstrate that the prenatal exposure to low doses of BPA perturbs mammary gland histoarchitecture and increases the carcinogenic susceptibility to a chemical challenge administered 50 days after the end of BPA exposure. ..
- Tsubura A, Lai Y, Miki H, Sasaki T, Uehara N, Yuri T, et al. Review: Animal models of N-Methyl-N-nitrosourea-induced mammary cancer and retinal degeneration with special emphasis on therapeutic trials. In Vivo. 2011;25:11-22 pubmed..In this review, the targets of MNU in various animal species are described, and special emphasis is given to therapeutic trials against MNU-induced mammary cancer and retinal degeneration in animal models. ..
- Takagi Y, Takahashi M, Sanada M, Ito R, Yamaizumi M, Sekiguchi M. Roles of MGMT and MLH1 proteins in alkylation-induced apoptosis and mutagenesis. DNA Repair (Amst). 2003;2:1135-46 pubmed..The haploinsufficient phenotype of Mlh1-heterozygous cells may be explained by competition in heterodimer formation between MLH1 homologues. ..
- Zulliger R, Lecaude S, Eigeldinger Berthou S, Wolf Schnurrbusch U, Enzmann V. Caspase-3-independent photoreceptor degeneration by N-methyl-N-nitrosourea (MNU) induces morphological and functional changes in the mouse retina. Graefes Arch Clin Exp Ophthalmol. 2011;249:859-69 pubmed publisher..MNU leads to the dose-dependent degeneration of photoreceptor cells in mice by caspase-3-independent pathways and is, therefore, a suitable model to study retinal degeneration in an animal model. ..
- Tokar E, Qu W, Liu J, Liu W, Webber M, Phang J, et al. Arsenic-specific stem cell selection during malignant transformation. J Natl Cancer Inst. 2010;102:638-49 pubmed publisher..The increased resistance to apoptosis and arsenite hyper-adaptability of WPE-stem cells suggests that arsenite transformation of RWPE-1 cells involves an increase in the number of CSC-like cells. ..
- Oka T, Nakajima T, Tamada Y, Shearer T, Azuma M. Contribution of calpains to photoreceptor cell death in N-methyl-N-nitrosourea-treated rats. Exp Neurol. 2007;204:39-48 pubmed..Oral calpain inhibitor SNJ-1945 may be a candidate for testing as a medication against retinal degeneration in retinitis pigmentosa. ..
- Russell L, Hunsicker P, Russell W. Comparison of the genetic effects of equimolar doses of ENU and MNU: while the chemicals differ dramatically in their mutagenicity in stem-cell spermatogonia, both elicit very high mutation rates in differentiating spermatogonia. Mutat Res. 2007;616:181-95 pubmedMutagenic, reproductive, and toxicity effects of two closely related chemicals, ethylnitrosourea (ENU) and methylnitrosourea (MNU), were compared at equimolar and near-equimolar doses in the mouse specific-locus test in a screen of all ..
- Gao Y, Deng X, Sun Q, Zhong Z. Ganoderma spore lipid inhibits N-methyl-N-nitrosourea-induced retinal photoreceptor apoptosis in vivo. Exp Eye Res. 2010;90:397-404 pubmed publisher..01). Taken together, these data suggest that GSL may regulate the expressions of Bax, Bcl-xl and Caspases-3, inhibiting MNU-induced rat photoreceptor cell apoptosis and protecting retinal function. ..
- Juchimiuk J, Hering B, Maluszynska J. Multicolour FISH in an analysis of chromosome aberrations induced by N-nitroso-N-methylurea and maleic hydrazide in barley cells. J Appl Genet. 2007;48:99-106 pubmed..Additionally, by using FISH with the same probes, an attempt was made to identify the origin of chromosome fragments in mitotic anaphase. ..
- Shibata W, Maeda S, Hikiba Y, Yanai A, Sakamoto K, Nakagawa H, et al. c-Jun NH2-terminal kinase 1 is a critical regulator for the development of gastric cancer in mice. Cancer Res. 2008;68:5031-9 pubmed publisher..Taken together, JNK seems to be involved in both tumor initiation and promotion and may be an attractive target for the prevention of gastric carcinogenesis. ..
- Kokkinakis D, Rushing E, Shareef M, Ahmed M, Yang S, Singha U, et al. Physiology and gene expression characteristics of carcinogen-initiated and tumor-transformed glial progenitor cells derived from the CNS of methylnitrosourea (MNU)-treated Sprague-Dawley rats. J Neuropathol Exp Neurol. 2004;63:1182-99 pubmed..initiated and malignant counterparts that were isolated from apparently normal brains of animals exposed to methylnitrosourea (MNU)...
- Hidaka M, Takagi Y, Takano T, Sekiguchi M. PCNA-MutSalpha-mediated binding of MutLalpha to replicative DNA with mismatched bases to induce apoptosis in human cells. Nucleic Acids Res. 2005;33:5703-12 pubmed..These observations imply that the induction of apoptosis is coupled with the progression of DNA replication through the action of PCNA. ..
- Homma K, Osakada F, Hirami Y, Jin Z, Mandai M, Takahashi M. Detection of localized retinal malfunction in retinal degeneration model using a multielectrode array system. J Neurosci Res. 2009;87:2175-82 pubmed publisher..This spatial information should be valuable in investigating local functional recovery in therapeutically treated areas, such as in gene transfer or cell transplantation. ..
- Maffini M, Soto A, Calabro J, Ucci A, Sonnenschein C. The stroma as a crucial target in rat mammary gland carcinogenesis. J Cell Sci. 2004;117:1495-502 pubmed..Our results suggest that the stroma is a crucial target of the carcinogen and that mutation in the Ha-ras-1 gene is neither necessary nor sufficient for tumor initiation. ..
- Komori K, Takagi Y, Sanada M, Lim T, Nakatsu Y, Tsuzuki T, et al. A novel protein, MAPO1, that functions in apoptosis triggered by O6-methylguanine mispair in DNA. Oncogene. 2009;28:1142-50 pubmed publisher..Both mouse and human MAPO1 proteins expressed in cells localize in the cytoplasm. We therefore propose that MAPO1 may play a role in the signal-transduction pathway of apoptosis induced by O(6)-methylguanine-mispaired lesions. ..
- Narisawa T, Fukaura Y. Prevention by intrarectal 5-aminosalicylic acid of N-methylnitrosourea-induced colon cancer in F344 rats. Dis Colon Rectum. 2003;46:900-3 pubmed..Eighty female F344 rats aged seven weeks received an intrarectal dose of 2 mg N-methylnitrosourea dissolved in 0.5 ml of water three times weekly for five weeks to induce colon cancer...
- Christov K, Grubbs C, Shilkaitis A, Juliana M, Lubet R. Short-term modulation of cell proliferation and apoptosis and preventive/therapeutic efficacy of various agents in a mammary cancer model. Clin Cancer Res. 2007;13:5488-96 pubmedThe methylnitrosourea (MNU)-induced mammary cancer model in rats is similar to estrogen receptor-positive breast cancer in women. In prevention studies using this model, tumor incidence and multiplicity were typically primary end points...
- Sakumi K, Shiraishi A, Shimizu S, Tsuzuki T, Ishikawa T, Sekiguchi M. Methylnitrosourea-induced tumorigenesis in MGMT gene knockout mice. Cancer Res. 1997;57:2415-8 pubmed..17: 1215-1220, 1996]. These MGMT-/- mice were most sensitive to the alkylating carcinogen, methylnitrosourea; when varied doses of methylnitrosourea were administered to 6-week-old mice and survivals at the 30th day ..
- Ogino H, Ito M, Matsumoto K, Yagyu S, Tsuda H, Hirono I, et al. Retinal degeneration induced by N-methyl-N-nitrosourea and detection of 7-methyldeoxyguanosine in the rat retina. Toxicol Pathol. 1993;21:21-5 pubmed..This finding suggests that the alkylation of the outer nuclear layer by MNU was the direct cause of the retinal degeneration seen in these animals. ..
- Kawate H, Sakumi K, Tsuzuki T, Nakatsuru Y, Ishikawa T, Takahashi S, et al. Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes. Proc Natl Acad Sci U S A. 1998;95:5116-20 pubmed..mutations in both alleles of the MGMT gene and one of the mismatch repair genes, MLH1, are as resistant to methylnitrosourea (MNU) as are wild-type mice, in terms of survival, but do have numerous tumors after receiving MNU...
- Medina D, Sivaraman L, Hilsenbeck S, Conneely O, Ginger M, Rosen J, et al. Mechanisms of hormonal prevention of breast cancer. Ann N Y Acad Sci. 2001;952:23-35 pubmed..in hormone-treated mammary cells is the initial proliferative burst induced by the chemical carcinogen methylnitrosourea. The decrease in proliferation is also accompanied by a decrease in the ability of estrogen receptor-..
- Jovtchev G, Stergios M, Schubert I. A comparison of N-methyl-N-nitrosourea-induced chromatid aberrations and micronuclei in barley meristems using FISH techniques. Mutat Res. 2002;517:47-51 pubmed..Combined with FISH it is also possible to elucidate the origin of MN and to discriminate between aneugenic and clastogenic effects. ..
- Swanson S, Unterman T. The growth hormone-deficient Spontaneous Dwarf rat is resistant to chemically induced mammary carcinogenesis. Carcinogenesis. 2002;23:977-82 pubmed..Taken together, these results demonstrate an important role for GH in alveolar development in the virgin rat, and provide the first direct evidence that GH plays a critical role in mammary carcinogenesis. ..
- Mabrouk G, Moselhy S, Zohny S, Ali E, Helal T, Amin A, et al. Inhibition of methylnitrosourea (MNU) induced oxidative stress and carcinogenesis by orally administered bee honey and Nigella grains in Sprague Dawely rats. J Exp Clin Cancer Res. 2002;21:341-6 pubmed..of bee honey and Nigella grains as nutraceuticals on the oxidative stress and carcinogenesis induced by methylnitrosourea (MNU) in Sprague Dawely rats. Four groups of animals were used and fed ad-libitum...
- Christov K, Ikui A, Shilkaitis A, Green A, Yao R, You M, et al. Cell proliferation, apoptosis, and expression of cyclin D1 and cyclin E as potential biomarkers in tamoxifen-treated mammary tumors. Breast Cancer Res Treat. 2003;77:253-64 pubmed
- Narisawa T, Fukaura Y. A noncarcinogenic small dose of n-methylnitrosourea enhances colon tumorigenesis in F344 rats. Tohoku J Exp Med. 2003;199:43-8 pubmed..This study was designed to investigate in F344 rats whether an intrarectal noncarcinogenic small dose of n-methylnitrosourea (0...
- Hamamoto Y, Hamamoto N, Nakajima T, Ozawa H. Morphological changes of epithelial rests of Malassez in rat molars induced by local administration of N-methylnitrosourea. Arch Oral Biol. 1998;43:899-906 pubmed..A mixture of N-methylnitrosourea (MNU) and alginate impression material for dental use was injected onto the periosteum of the buccal side of ..
- Lu J, Pei H, Kaeck M, Thompson H. Gene expression changes associated with chemically induced rat mammary carcinogenesis. Mol Carcinog. 1997;20:204-15 pubmed..The genes identified in this study may therefore represent mammary carcinoma-specific molecular markers that may be helpful in investigations of mammary carcinogenesis and its prevention. ..
- Thordarson G, Van Horn K, Guzman R, Nandi S, Talamantes F. Parous rats regain high susceptibility to chemically induced mammary cancer after treatment with various mammotropic hormones. Carcinogenesis. 2001;22:1027-33 pubmed..0%, respectively; a tumor incidence similar to that of untreated AMV rats (64%). Parous rats treated with E2 plus P4 had tumor incidence higher than 90%. T4 administered did not affect mammary carcinogenesis. ..
- Richardson K, Richardson F, Crosby R, Swenberg J, Skopek T. DNA base changes and alkylation following in vivo exposure of Escherichia coli to N-methyl-N-nitrosourea or N-ethyl-N-nitrosourea. Proc Natl Acad Sci U S A. 1987;84:344-8 pubmed..Of the G X C----A X T transitions, 82% of the MNU- and 71% of the ENU-induced mutations occurred at the middle guanine of the sequence 5'-GG(A or T)-3'. ..
- Narisawa T, Fukaura Y, Hasebe M, Nomura S, Oshima S, Inakuma T. Prevention of N-methylnitrosourea-induced colon carcinogenesis in rats by oxygenated carotenoid capsanthin and capsanthin-rich paprika juice. Proc Soc Exp Biol Med. 2000;224:116-22 pubmed..008 mg capsanthin six times a week for Weeks 2-6 after receiving three intrarectal doses of 4 mg N-methylnitrosourea in Week 1...
- Thompson H, McGinley J, Rothhammer K, Singh M. Ovarian hormone dependence of pre-malignant and malignant mammary gland lesions induced in pre-pubertal rats by 1-methyl-1-nitrosourea. Carcinogenesis. 1998;19:383-6 pubmed
- Lubet R, Steele V, DeCoster R, Bowden C, You M, Juliana M, et al. Chemopreventive effects of the aromatase inhibitor vorozole (R 83842) in the methylnitrosourea-induced mammary cancer model. Carcinogenesis. 1998;19:1345-51 pubmed..activity of the highly specific nonsteroidal aromatase inhibitor, vorozole, was examined in the methylnitrosourea (MNU)-induced rat model of mammary carcinogenesis. Various doses of vorozole (0.08-1...
- Medina D, Peterson L, Moraes R, Gay J. Short-term exposure to estrogen and progesterone induces partial protection against N-nitroso-N-methylurea-induced mammary tumorigenesis in Wistar--Furth rats. Cancer Lett. 2001;169:1-6 pubmed..The significance of these results are discussed in terms of the contradictory results in the literature and the role of morphological differentiation in conferring the protective effect. ..
- Rajkumar L, Guzman R, Yang J, Thordarson G, Talamantes F, Nandi S. Short-term exposure to pregnancy levels of estrogen prevents mammary carcinogenesis. Proc Natl Acad Sci U S A. 2001;98:11755-9 pubmed
- Asakura S, Daimon H, Sawada S, Sagami F. A short-term assessment of tumor-promotion activity in the livers of rats treated with two genotoxic methylating agents: dimethylnitrosamine and methylnitrosourea. Toxicol Lett. 1998;98:155-67 pubmed..of F344 rats exposed in vivo to the methylating agents dimethylnitrosamine (DMN, hepatocarcinogen) and methylnitrosourea (MNU, non-hepatocarcinogen)...
- Tsuzuki T, Sakumi K, Shiraishi A, Kawate H, Igarashi H, Iwakuma T, et al. Targeted disruption of the DNA repair methyltransferase gene renders mice hypersensitive to alkylating agent. Carcinogenesis. 1996;17:1215-20 pubmed..Administration of methylnitrosourea to these gene-targeted mice led to early death, and normal mice treated in the same manner showed no ..
- Ohgaki H, Fukuda M, Tohma Y, Huang H, Stoica G, Tatematsu M, et al. Effect of intragastric application of N-methylnitrosourea in p53 knockout mice. Mol Carcinog. 2000;28:97-101 pubmed..In this study, p53(-/-), p53(+/-), and p53 wild-type (p53(+/+)) mice were treated with N-methylnitrosourea (MNU) by gastric intubation (5 microg/g body weight) three times per week for 5 wk, starting at 5-6 wk of ..
- Zhou H, Liu L, Lee K, Qin X, Grasso A, Kung H, et al. Lung tumorigenesis associated with erb-B-2 and erb-B-3 overexpression in human erb-B-3 transgenic mice is enhanced by methylnitrosourea. Oncogene. 2002;21:8732-40 pubmed..latency was shorter and the incidence higher in erb-B-3 transgenic mice treated with the methylating agent, methylnitrosourea [MNU]...
- Desaulniers D, Leingartner K, Russo J, Perkins G, Chittim B, Archer M, et al. Modulatory effects of neonatal exposure to TCDD, or a mixture of PCBs, p,p'-DDT, and p-p'-DDE, on methylnitrosourea-induced mammary tumor development in the rat. Environ Health Perspect. 2001;109:739-47 pubmed..groups, except for a control group and a 1,000-mix group, received a single intraperitoneal injection of methylnitrosourea (MNU, 30 mg/kg bw), the initiator of the carcinogenic process...