Disease relevance of CCRIS 2072

• Conversion to propane 2-nitronate (P2N), the anion of the tautomeric aci form of 2-NP, seems to be a pivotal part of the mechanism by which 2-NP causes its toxicity [1].

High impact information on CCRIS 2072

• Human phenol sulfotransferases hP-PST and hM-PST activate propane 2-nitronate to a genotoxicant [2].
• The genotoxicity of the compound in rats has been attributed to sulfotransferase-mediated formation of DNA-reactive nitrenium ions from the anionic form of 2-NP, propane 2-nitronate (P2N) [2].
• Acetoxime is metabolized by human and rodent hepatic cytochrome P450 enzymes to the genotoxicant and carcinogen propane 2-nitronate [3].
• The chemistry of the nonenzymatic oxidation of the rat liver carcinogen, 2-nitropropane, and its anionic form, propane-2-nitronate, was investigated using pulse radiolysis and EPR/spin trapping with 3,5-dibromo-4-nitrosobenzenesulfonic acid as the trapping agent [4].
• Activation of propane 2-nitronate to a genotoxicant in V79-derived cell lines engineered for the expression of rat hepatic sulfotransferases [5].

Biological context of CCRIS 2072

• Equilibrium formation, hydrolysis and reduction of nitronates were pH-dependent and, in the case of propane 2-nitronate, yielded mainly acetone, nitrite and acetone oxime, apart from 2-nitropropane [6].

Anatomical context of CCRIS 2072

• All three species showed UDS after exposure of hepatocytes to propane 2-nitronate at 0.1 mM although the effect in human cells was variable [7].
• Sulfotransferase-mediated genotoxicity of propane 2-nitronate in cultured ovine seminal vesicle cells [8].
• Optical difference spectra were recorded in mixtures of propane-2-nitronate with liver microsomes from phenobarbital-pretreated rats [9].
• Lymphocyte 8OHdG/dG was not affected significantly by 2NP, TCE or PERC [10].
• To that end 2-NP or propane-2-nitronate were incubated with murine hepatic microsomes at concentrations of up to 10 mM, and generation of nitrite was measured as product of metabolic oxidation of the two species [9].

Gene context of CCRIS 2072

• The results demonstrate that propane-2-nitronate, like 2-NP, undergoes microsomal oxidative denitrification, probably catalysed by cytochrome P-450 [9].
• Induction of gamma GT- and GST-P positive foci in the liver of rats treated with 2-nitropropane or propane 2-nitronate [11].

Analytical, diagnostic and therapeutic context of CCRIS 2072

• The mutagenicity correlated with an enhanced rate of tautomerase to propane 2-nitronate at relatively high pH as measured by high performance liquid chromatography [12].
• The pKa of the reaction 2-nitropropane less than--greater than propane 2-nitronate measured by HPLC was 7.63 [6].
• A positive control group received 100 mg/kg 2-nitropropane (2NP) [10].

References