Metabolism and genotoxicity of carcinogenic phenylpropanoids naturally occuring in food

苯丙素是天然存在的植物成分。其中一些，如黄樟酚和甲基丁香酚已被列为遗传毒性致癌物。迄今为止，人们对菖蒲精油中α -、β -和γ -细辛酮的致癌性机制知之甚少。由于缺乏烯丙基侧链，最终烯丙基致癌代谢物形成的关键机制不能转移到α -和β -细辛酮中。由于细辛酮同分异构体的代谢数据有限，以及细辛酮代谢物的遗传毒性和致突变性数据缺乏，迄今为止还没有对母体化合物的毒性谱进行机制分类。2005年，欧洲理事会调味物质专家委员会对-细辛酮进行了评估，并指出有必要进一步研究-细辛酮致癌性的作用机制，特别是对-细辛酮是否具有遗传毒性的问题进行研究。本研究的目的是在包括人类在内的不同物种的体外实验模型中研究三种细辛酮异构体的代谢。这些将用于研究和表征细辛烷及其代谢物的遗传毒性和致突变特性，以评估它们对母体化合物的毒性和致癌性的贡献。

Phenylpropanoids are naturally occurring plant constituents. Some of them, e.g. safrole and methyleugenol have already been classified as genotoxic carcinogens. Little is known so far about the mechanism of carcinogenicity of alpha-, beta-, und gamma-asarone, which are found in essential oils of Acorus calamus und A. gramineus. The crucial mechanism of formation of an ultimate allylic carcinogenic metabolite described for safrole and others, is not transferable to alpha- and beta-asarone, due to the lack of an allylic side chain. Because of the limited metabolism data for asarone isomers and the lack of data on genotoxicity and mutagenicity of asarone metabolites, no mechanistic classification of the toxic profile of the parent compounds could been implemented so far. The Committee of Experts on Flavouring Substances of the Council of Europe evaluated beta-asarone in 2005 and pointed out the need for further studies on the mechanism of action of (beta-)-asarone carcinogenicity in particular for studies addressing the question whether beta-asarone is genotoxic or not. The aim of this research project is to investigate the metabolism of the three asarone isomers in experimental in vitro models from different species including humans . These will be used to investigate and characterize the genotoxic and mutagenic properties of asarones and their metabolites in order to assess their contribution to the toxicity and carcinogenicity of the parent compounds.