Disease relevance of nitramide

• Lifetime tests were done in NZR inbred rats of dimethylnitramine (DMNO) by addition to the drinking water (average dose 1.83 g/kg body weight) and in NZO mice by repeated subcutaneous injection from birth to 7 months of age followed by administration in drinking water (total average dose 4.72 g/kg body weight) [1].
• The toxicity of single doses of N-nitrodimethylamine in rodents [2].
• N-Nitrodimethylamine was found to be mutagenic to Salmonella typhimurium TA100 when applied at above 200 mumol/plate with metabolic activation [3].

High impact information on nitramide

• Large doses of dimethylnitramine (DMNM), N-nitroso-L-proline (NPRO), and sodium nitrite were administered in the drinking water to MRC Wistar rats for at least 1 year, and the rats were maintained for life [4].
• Formaldehyde as a possible mutagenic metabolite of N-nitrodimethylamine and of other agents which are suggested to yield non-alkylating species in vitro [5].
• Hydroxylation and nitroreduction are required to activate dimethylnitramine into alkylating and mutagenic agents [6].
• DNA damage in liver of mice treated with N-nitrodimethylamine [7].
• The structures and energies of the reactants, products, and transition states of the initial steps in the gas-phase decomposition of dimethylnitramine (DMNA) have been determined by quantum chemical calculations at the B3LYP density-functional theory, MP2, and G2 levels [8].

Biological context of nitramide

• Upon nitrosation in artificial saliva, these amines produced not only the related N-nitrosamines but also relatively high levels of the corresponding nitramines--N-nitrodibutylamine (NTDBA), N-nitrodiethylamine (NTDEA) and N-nitrodimethylamine (NTDMA) [9].

Anatomical context of nitramide

• N-Nitrodimethylamine (NTDMA) was found to be a carcinogen of the nasal mucosa leading to aesthesioneuroepitheliomas in BDVI rats [10].
• Subcellular fractions of rat organs contain nitroreductases which reduce N-nitrodimethylamine to N-nitrosodimethylamine [11].

References