Disease relevance of methylurea

• A dose-response effect of NMU at 10, 20, 30, 40, and 50 mg/kg body weight was also studied in groups of rats fed an HF or an LF diet [1].
• Sodium ascorbate (NaASC) at the highest level tested (11.5 or 23 g/kg food) gave 89-98% inhibition of adenoma induction by the NaNO2 plus piperazine, morpholine, and methylurea systems [2].
• When the injections of NMU were started in males at age 100 days, a specific dyad of neoplastic growths was evoked that consisted of primary myelocytic leukemia and ear duct cancer, whereas mammary cancer and other neoplasms were not evident [3].
• In addition, these cells had less than 10 percent hemolysis when suspended in 2 M methylurea prepared in 0.4 percent phosphate-buffered saline (pH 7.2) [4].
• The present study indicates that DMTU as well as another growth inhibitory methylurea derivative, tetramethylurea (TMU) significantly decrease ATP content in the B16 melanoma cell line [5].

Psychiatry related information on methylurea

• The latency period, NMU-induced tumour incidence and the number of tumours per rat in diabetic rats versus controls were 117 +/- 7 days versus 79 +/- 9 days (P < 0.001); 93% versus 95% (NS); and 5.2 +/- 1.6 versus 2.7 +/- 0.5 (P < 0.02) [6].

High impact information on methylurea

• When the injections of NMU were started in weanling male rats, a specific triad of neoplasms developed that consisted of mammary carcinoma, primary myelocytic leukemia, and ear duct cancer [3].
• DMH (80 mg/kg) was the most effective at inducing acute cell death and this was closely followed by NMU (200 mg/kg) [7].
• 2. The permeabilities to urea, thiourea and to N-methylurea (about 10(-6) cm/sec at 25 degrees C) were independent of concentration within a very broad range, and we found no evidence of interaction between transport of analogue molecules [8].
• OBJECTIVE: The aim of the present work was to examine whether in utero exposure to BPA alters mammary gland development and increases its susceptibility to the carcinogen N-nitroso-N-methylurea (NMU) [9].
• Immature kidneys, which preferentially developed nephroblastomas after NMU treatment, also displayed significantly lower MGMT activity than mature kidneys [10].

Chemical compound and disease context of methylurea

• Recently, we have demonstrated the malignant transformation of HPV-18 C-1 cells after multiple exposures to the chemical carcinogen N-nitroso-N-methylurea (NMU) [11].
• The effect of short intermittent light exposures on the melatonin circadian rhythm and NMU-induced breast cancer in female F344/N rats [12].
• Oral administration of coffee at doses ranging from 150 mg to 1 g per kg body weight significantly decreased endogenously formed nitrosourea-mediated DNA damage in bone marrow as well as in colon epithelial cells in mice that had simultaneously received oral administration of methylurea and sodium nitrite [13].

Biological context of methylurea

• The incidence of Ha-ras gene mutation was 79% (27 of 34) at codon 12 in the NMU group and 23% (nine of 40) at codon 61 in the DMBA group [14].
• The addition of GTP during and after nitrosation of methylurea resulted in a dose-dependent inhibition of mutagenicity [15].
• Methylurea did not alter water permeability or transmembrane electrical resistance [16].
• The metabolites result from aromatic ring hydroxylation, oxidation, and dealkylation of the urea methyl group, and oxidative ring opening of the pyrrolidine ring [17].
• Catechu extract and catechin inhibited the nitrosation of methylurea by nitrite at pH 3.6 and 30 degrees C. The formation of nitrosomethylurea in the reaction mixture was monitored by measuring the histidine revertants of strain TA 1535 in the absence of metabolic activation [18].

Anatomical context of methylurea

• The work reported here was undertaken to better define this age-specific susceptibility of the mammary gland to NMU [10].
• In contrast, the permeability of the oral mucosa to ethylurea and propylurea was less than to methylurea [19].
• Using human red cell membranes, in which the osmotic flow is dominated by Aquaporin-1, we show here that compared to NaCl the reflexion coefficient of the channel for methylurea, when corrected for solute volume exchange and for the water permeability of the lipid membrane, is 0.54 [20].
• The nitrosation of methylurea was used as a model because the nitrosation products can be readily detected by their mutagenic (his+ revertants of S. typhimurium) and clastogenic (chromosome aberrations in CHO cells) properties [21].
• Furthermore, enlargement of the intramammary lymph nodes with prominent mast cells was observed in NMU treated COP rats, but not in NMU treated BUF rats [22].

Associations of methylurea with other chemical compounds

• Carcinogenicity of methylurea or morpholine in combination with sodium nitrite in rat multi-organ carcinogenesis bioassay [23].
• For carcinogenic risk assessment of combinations of N-nitroso precursors in man, the effects of feeding methylurea (MU) or morpholine (Mor) plus sodium nitrite (NaNO2) were investigated using a multi-organ carcinogenesis model [23].
• Eugenol and the plant extracts also inhibited the nitrosation of methylurea in a dose-dependent manner [24].
• Nitrosation of methylurea was inhibited by thiols, polyphenols, alcohols, sorbic acid, dl-alpha-tocopherol etc., due to possibly competition for available nitrite [25].
• These effects are explained in terms of increased polarity of the medium and the adsorption ability of urea/monomethylurea on the charged surfactant monomers of the micelle [26].

Gene context of methylurea

• To determine whether p53 alterations, which are frequent in human breast cancers, are also common in rat mammary tumors, we examined 40 tumors from 24 rats treated with 7,12-dimethylbenz[a]anthracene (DMBA) and 34 tumors from 14 rats treated with N-nitroso-N-methylurea (NMU) (an N-nitroso compound) [14].

Analytical, diagnostic and therapeutic context of methylurea

• Using the alkaline comet assay, it was found that MECs from immature but not mature rats displayed an increase in single-strand DNA breaks or alkali-labile lesions 2 h following NMU treatment [10].
• The results showed that IGF-IR is present in NMU tumors (analyzed by binding assay and Western blot), that a variable content is expressed in tumors that continued growing post-ovariectomy (OVX) of rats, and that it is undetectable in tumors that regressed post-OVX [27].
• With the low-protein diet, the amount of NMU after 1 hour was 36.6 micrograms, corresponding to 5.3% conversion of methylurea [28].
• Mammary adenocarcinomas were induced by a single intravenous injection of N-nitroso N-methylurea [29].
• Group 1, 2 and 3 each received two intraperitoneal injections of the carcinogen N-nitroso-N-methylurea (NMU): 50 mg/Kg BW [30].

References