Genotoxicity of methyleugenol and selected oxidative metabolites
Methyleugenol is a natural alkenylbenzene found in cosmetics, soaps, shampoos, fragrances, and herbal products. It has been classified as a naturallyoccurring genotoxic carcinogen compound with DNAbinding potency by the Scientific Committee on Food in 1999. The cytochrome P450 (CYP450) catalyzed hydroxylation of the benzylic carbon of the alkenyl side chain and the formation of an unstable sulfate ester derivative have been discussed as key events of genotoxicity. We addressed the question whether several phase I metabolites of methyleugenol formed by incubations with liver microsomes exhibit DNA strand breaking properties and whether these effects contribute to the genotoxicity of the parent compound. As cell model we used V79 cells lacking CYP450 and sulfotransferase activity.
Cytotoxicity, genotoxicity and mutagenicity of cyclopentenon prostglandins
Prostglandins are characterized as potent eicosanoid lipid mediators that are involved in numerous cellular processes and inflammation. At the first step prostglandin H2 (PGH2) is formed by the bis-oxygenation of arachidonic acid catalyzed by cyclooxygenases and serves as the precursor to all prostanoid products formed, including prostaglandins, prostacyclins, and thromboxanes. A dehydration of the hydroxyl groups of PGH2 lead to α, β-and α,γ-unsaturated carbonyl compounds.The α, β-unsaturated carbonyl compounds react with SH-groups of amino acids in a Micheal addition associated with an activation of cellular signal cascades contribute to the observed antiinflammatory, antineoplastic and antiviral effects of cyclopentenon prostaglandins. However, little is known so far about potential cytotoxic, genotoxic or mutagenic effects of these compounds. In our studies celluar biomarkers associated with inflammatory-mediated carcinogenes should be characterized.