Disease relevance of Dimethylnitrosamine

• In murine liver fibrosis models using dimethylnitrosamine, mice with haploinsufficiency of the SOCS1 gene (SOCS1(-/+) mice) developed more severe liver fibrosis than did wild-type littermates (SOCS1(+/+) mice) [1].
• The morphologic character of kidney cells during serial subculture following isolation from Wistar rats treated several hours to 1 week previously with a carcinogenic dose of dimethylnitrosamine (DMN; 60 mg/kg body weight following protein deprivation) was compared with the appearance of cultures derived from normal control rats [2].
• Carcinogenicity and acute toxicity of dimethylnitrosamine in rainbow trout (Salmo gairdneri) [3].
• During experiments to study the evolution of hepatocellular carcinoma in adult male Wistar rats by exposing regenerating livers to the action of small doses of dimethylnitrosamine (DMN) or N-2-acetylaminofluorene (AAF), several primary sarcomas of the liver were incidentally observed [4].
• However, diethylnitrosamine and dimethylnitrosamine, which do not induce stomach cancer in rats, did not cause any decrease in pepsinogen content [5].

Psychiatry related information on Dimethylnitrosamine

• Volatile nitrosamines were determined in alcoholic drinks during epidemiologic studies on the relationship between esophageal cancer incidence and alcohol consumption in Normandy, France. Nitrosodimethylamine (NDMA) was found commonly in most alcoholic drinks tested, with the exception of wine [6].
• Because N-nitrosodimethylamine is a procarcinogen, the possibility that induction of P-450 2E1 by alcohol abuse may accelerate the carcinogenic action of a very small dose of N-nitrosodimethylamine should be considered [7].
• The effects of various dietary modifications on the mutagenicity of dimethylnitrosamine (DMNA), N-nitrosomorpholine, and N-methyl-N-nitrosourea for Salmonella typhimurium his G-46 in the host-mediated assay were studied [8].
• Dimethylnitrosamine (DMN) exposure altered the activity of the macrophage and natural killer (NK) cell defense mechanisms against the B16F10 melanoma in B6C3F1 adult female mice as assessed by several immunologic assays [9].
• The length of the latency period of hepatocellular tumors in individual rats was negatively related to the activities of hepatic dimethylnitrosamine N-demethylase, aryl hydrocarbon hydroxylase and epoxide hydrolase and positively related to the amount of microsomal protein [10].

High impact information on Dimethylnitrosamine

• Heterozygous mice treated with a liver carcinogen, dimethylnitrosamine, showed a decreased survival time in comparison to treated wild type mice, suggesting that the p53-deficient mice may be useful for some in vivo carcinogenesis assays [11].
• Generation of dimethylnitrosamine in water purification systems. Detection in human blood samples during hemodialysis [12].
• We examined N-nitrosodimethylamine-induced kidney tumors of the clear or mixed clear/granular cell type in Wistar rats to assess the presence of VHL mutations [13].
• We measured levels of N-nitrosodimethylamine (NDMA) in peripheral blood from 13 fasting male patients, 30-74 years old, who had chronic renal failure, and in five healthy control subjects (four males and one female) 31-50 years old [14].
• This activation system was found a) to be only minimally cytotoxic by itself and b) to be able to mediate NADPH-dependent, dose-dependent toxicity, and transformation by activating the procarcinogens dimethylnitrosamine, 2-naphthylamine, 2-aminoanthracene, and aflatoxin B1 [15].

Chemical compound and disease context of Dimethylnitrosamine

• The early stages of dimethylnitrosamine (CAS: 62-75-9)-induced liver cancer and the effect of administration of phenobarbital (CAS: 50-06-6) after dimethylnitrosamine were studied in Syrian golden hamsters [16].
• Methyl(acetoxymethyl)nitrosamine (DMN-OAc) was synthesized and tested for toxicity and carcinogenicity in rats to test the hypothesis that alpha-hydroxylation is required for metabolic activation of dimethylnitrosamine (DMN) to a reactive, proximate carcinogen [17].
• On omeprazole, Helicobacter pylori-positive vs. -negative patients had a nonsignificantly higher intragastric nitrite level and higher urinary N-nitrosodimethylamine excretion [18].
• We present the assay protocol, the concentration-dependent toxicity and mutagenicity of five known mutagens (N-methyl-N'-nitro-N-nitrosoguanidine, ICR-191, 9-aminoacridine, dimethylnitrosamine, and benzo[a]pyrene), and reconstruction experiments testing the assay for possible bias [19].
• To investigate the effect of liver injury on the removal and the production of acetaldehyde, we produced fibrosis and cirrhosis (by chronic administration of carbon tetrachloride) and fatty liver (with very small doses of dimethylnitrosamine) in rats [20].

Biological context of Dimethylnitrosamine

• DNA alkylation and tumor induction in regenerating rat liver after cell cycle-related continuous N-nitrosodimethylamine infusion [21].
• Effect of protein diet on age-dependent methylation of liver nuclear components of mice administered N-nitrosodimethylamine [22].
• The oxidative dealkylation of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), and methylethylnitrosamine (MEN) by Sprague-Dawley rat liver microsomes was studied by a colorimetric assay for the simultaneous analysis of formaldehyde and acetaldehyde [23].
• The histology of a spontaneously occurring neoplasm of the rat kidney conforming to a classification of nephroblastoma is described and compared with that of N-nitrosodimethylamine-induced renal mesenchymal tumors [24].
• Oxidative demethylation of dimethylnitrosamine (DMN) was detectable with liver homogenate preparations from fetal mice (noninbred Swiss) by day 16 of gestation; this activity increased to adult levels by postnatal day 7 [25].

Anatomical context of Dimethylnitrosamine

• Inhibition of dimethylnitrosamine-induced strand breaks in liver DNA and liver cell necrosis by diethyldithiocarbamate [26].
• Effects of oxygen depletion on in vitro metabolism of dimethylnitrosamine in microsomes from rat liver and human tissues [27].
• The rates of N-demethylation of dimethylnitrosamine and dimethylnitrosamine-d6 by rat liver microsomes were studied by monitoring formaldehyde production [28].
• Four 1-theta-D-arabinofuranosylcytosine (ara-C)-and one dimethylnitrosamine-transformed Syrian hamster cell lines were established [29].
• In vivo liver fibrosis was induced by dimethylnitrosamine administration and bile duct ligation (BDL) in rats treated or not treated with amiloride [30].

Associations of Dimethylnitrosamine with other chemical compounds

• When nursing Sprague-Dawley rats were treated with [14C]N-nitrosodimethylamine [(NDMA) CAS: 62-75-9], N-nitrosopyrrolidine (CAS:930-55-2), or N'-nitrosonornicotine (CAS: 16543-55-8), the liver and kidney DNA from their 14-day-old offspring that had been nursed over a 24-hour period became labeled [31].
• An acute 4-hour in vitro exposure to 0.5 mM of the colon-selective carcinogens 1,2-dimethylhydrazine dihydrochloride (DMH) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) produced 26 and 78% suppressions of replicative DNA synthesis, respectively, whereas the same exposure to the liver carcinogen dimethylnitrosamine produced only a 5% suppression [32].
• Protein diets deficient or enriched in DL-methionine were studied for the effect of methylation of nuclear components in subadult and adult outbred albino male mice given N-nitrosodimethylamine [22].
• alpha-Hydroxylation pathway in the in vitro metabolism of carcinogenic nitrosamines: N-nitrosodimethylamine and N-nitroso-N-methylaniline [33].
• This finding is consistent with previous reports that the half-life of 7-methylguanine in DNA after treatment with the carcinogen dimethylnitrosamine is longer in rats than in hamsters [34].

Gene context of Dimethylnitrosamine

• Dimethylnitrosamine (6 mg/kg body weight) induced lung tumors (adenomas and carcinomas) in 100% of Fhit-/-Vhl+/- mice and adenomas in 40% of Fhit-/- mice by 20 months of age [35].
• All these results emphasize that the catalytic site of P450 2EI has a geometric configuration such that only small molecules like nitrosodimethylamine fit favorably within the putative active site of the enzyme [36].
• By using 10 heterologously expressed P450s, it was shown that nitrosodimethylamine was mainly demethylated by CYP2E1 [36].
• Oesophageal microsomes activated N-nitrosodimethylamine with a low degree of inter-individual variation and microsomes prepared from the tumour of a patient who strongly expressed CYP2A6/2A7 mRNA activated N-nitrosodiethylamine [37].
• ERK1/2, JNK and p70(S6K) activation was associated with hepatocytes proliferation after DMN, while JNK activation was not associated with cholangiocytes proliferation after BDL [38].

Analytical, diagnostic and therapeutic context of Dimethylnitrosamine

• Over the course of 20 weeks, Sprague-Dawley rats developed intestinal tumors in response to an intraperitoneal injection of the acetate derivative of dimethylnitrosamine [39].
• Production of kidney tumors in rats with low dose of dimethylnitrosamine after partial hepatectomy [40].
• Distinctive patterns of proliferative activity in kidney cell cultures derived from normal dimethylnitrosamine-treated, and renal tumor-bearing rats [41].
• Cocultivation of the liver cells and V79 cells in the presence of the carcinogens N-nitrosodimethylamine, N-nitrosodiethylamine, and aflatoxin B1 caused the induction of ouabain-resistant mutants of V79 cells [42].
• Mechanistic and statistical insight into the large carcinogenesis bioassays on N-nitrosodiethylamine and N-nitrosodimethylamine [43].

References