Disease relevance of Ortard

• Mutagenic activity and specificity of N-nitrosomethylaniline and N-nitrosodiphenylamine in Salmonella [1].

High impact information on Ortard

• During the treatment of outbred Sprague-Dawley rats with methylnitrosourea (MNU) or the noncarcinogenic analog diphenylnitrosamine, antibody levels to teichoic acid as well as several parameters of lymphocyte and macrophage function were assessed in animals not overtly stimulated with antigen [2].
• With both techniques DNA damage was undetectable in liver of rats treated with 540 mg/kg of the non-hepatocarcinogen N-nitrosodiphenylamine [3].
• Most were either carcinogenic via a non-genotoxic mechanism (liver enzyme inducers, peroxisome proliferators, hormonal carcinogens) considered not necessarily relevant for humans, or were extremely weak (presumed) genotoxic carcinogens (e.g. N-nitrosodiphenylamine) [4].
• Paclitaxel and the internal standard (IS, N-nitrosodiphenylamine) were separated on a 10-microns particle, 8 mm x 10 cm C18 cartridge in conjunction with a radial compression system preceded by Guard Pak with a C18 insert [5].
• The genetic toxicology of N-nitrosodiphenylamine [6].

Biological context of Ortard

• Pharmacokinetics of biliary excretion of N-nitrosodiphenylamine (NDPA) in animals of different species [7].

Anatomical context of Ortard

• Nitrosodiphenylamine was tested for induction of DNA single strand breaks in rat hepatocytes and Chinese hamster V 79 cells with the alkaline filter elution assay [8].
• The study shows that superoxide radical which is generated by NADPH-cytochrome c reductase is involved in the oxidation of 1,1-diphenylhydrazine to N-nitrosodiphenylamine catalyzed by rat liver microsomes [9].
• The carcinogenic nitrosamines, N-nitrosomethylaniline (NMA) and N-nitrosodiphenylamine (NDphA), which have been previously reported negative or very weakly mutagenic in the Salmonella/microsome assay, were found to be mutagenic in the hisG428 Salmonella strain, TA104 [1].
• A major proportion of bacterial types, common in the gastrointestinal tract of many animals and man, were active in degrading diphenylnitrosamine and dimethylnitrosamine, the former being degraded more rapidly than the latter [10].
• Pharmacokinetic investigations into the biliary excretion of N-nitrosodiphenylamine given as an i.p. dose of 50 mg/kg were conducted and results compared in three animal species; rat, guinea pig and rabbit following bile duct cannulation and collection of bile in vitro [7].

Associations of Ortard with other chemical compounds

• Therefore the metabolism of nitrosodiphenylamine was investigated in phenobarbital-induced mouse liver microsomes and some of the metabolites were also tested [8].
• Reduction of N-nitrosodiphenylamine to the corresponding hydrazine by guinea pig liver preparations [11].
• RM 8107 provides reference values obtained by LC analysis for the key additives nitroglycerin, diphenylamine (and its nitration product, N-nitrosodiphenylamine), and ethylcentralite [12].

Gene context of Ortard

• In view of the metabolic capacity of hepatocytes and the chemical structure of nitrosodiphenylamine it seems likely that cytochrome P-450-dependent, reductive denitrosation might be necessary for exerting this effect [8].
• Diphenylnitrosamine also decreased cytochrome P-450 by 54%, AHH activity by 64% but increased the activity of DMN-dI by 42%, the cytochrome b5 content by 159% and NADPH-cytochrome c reductase activity by 57% [13].
• Substantial enhancement of the induction of DNA damage was however, restricted to NDEA, NPYR and NMOR, whereas with nitrosodiphenylamine (NDPhA), NDELA and NDMA only a moderate (less than 25%) increase of differential killing effects was found [14].

References