Abstract 5549: Formation of propylamine during peroxidation of the tobacco alkaloid Myosmine

Abstract

Abstract The alkaloid myosmine is widespread in the biosphere including food materials and tobacco. Its activation in vitro and in vivo, especially in biological systems, is documented by per-oxidation, CYP 450 systems and N-nitrosation procedure. As reported, activation of tobacco specific N-nitrosamines (TSNA) N’-nitroso-nornicotine (NNN) and 4-(methylnitros-amino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanole (NNAL) leads to hydroxypyridylbutanone (HPB) which is also generated in case of myosmine by N-nitrosation, peroxidation and in rat experiments. The precursor of HPB is the highly reactive intermediate species POB which is assumed to be responsible for DNA-adducts causing tumorigenesis and cancer. Additionally, during peroxidation procedure from myosmine and in metabolic studies with rats compound 3-carbinol was detected. Activation via peroxidation of the alkaloid is performed at the C=N pyrrolidine-ring position preferentially leading to unstable oxirane formation. Subsequently decay between 2’-and 3’position takes place yielding 3-carbinol. Further degradation products of the pyrrolidine-oxirane decay were not known till now, but could be high-reactive intermediates. In our investigations we detected the amino propyl-moiety as additional fragment from pyrrolidine oxirane ring decay. Therefore, during myosmine peroxidation generation of two high-reactive species appear to be plausible. Either 3-picolyl derivative could lead to 3-carbinol and subsequently to nicotinic acid, or other fragment, the propylamino-intermediate reacts to the corresponding amine. Existence of 3-carbinol was reported by myosmine-peroxidation, but elucidating the postulated new propyl-amino pathway is in focus of our current interest. Myosmine was peroxidated by hydro-genperoxide as reported earlier and the formed propylamine amount could be directly de-rivatized by dansylchloride. The derivatised amine (dansylated propylamine) was analysed with high pressure liquid chromatography (HPLC) instrumentation using fluorescence detection with excitation at 320 nm and emission at 500 nm. Retention times were compared by analysis of reference substances. Possibility of myosmine activation to high-reactive amine derivatives with peroxides allows conversion of the substance under influence of ROS (reactive oxygen species). This new activation pathway may result in interaction of the propylamino-mojety with proteins, cell-receptors or DNA. A possible carcinogenic risk of myosmine uptake by humans could not be excluded. Further experiments are demanded to elucidate the new pathway in view of a possible carcinogenic risk of myosmine. Acknowledgement: This work was supported by DFG grant Zwi59/2-2, and TY 81/1-2 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5549. doi:10.1158/1538-7445.AM2011-5549