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Urinary Excretion of Mercapturic Acids of the Rodent Carcinogen Methyleugenol after a Single Meal of Basil Pesto: A Controlled Exposure Study in Humans.
Nieschalke, Kai; Bergau, Nick; Jessel, Sönke; Seidel, Albrecht; Baldermann, Susanne; Schreiner, Monika; Abraham, Klaus; Lampen, Alfonso; Monien, Bernhard H; Kleuser, Burkhard; Glatt, Hansruedi; Schumacher, Fabian.
Afiliação
  • Nieschalke K; Department of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany.
  • Bergau N; Department of Food Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany.
  • Jessel S; Department of Food Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany.
  • Seidel A; Biochemical Institute for Environmental Carcinogens, Prof. Dr. Gernot Grimmer-Foundation, 22927 Grosshansdorf, Germany.
  • Baldermann S; Biochemical Institute for Environmental Carcinogens, Prof. Dr. Gernot Grimmer-Foundation, 22927 Grosshansdorf, Germany.
  • Schreiner M; Department Plant Quality and Food Security, Leibniz Institute of Vegetable and Ornamental Crops (IGZ), 14979 Grossbeeren, Germany.
  • Abraham K; Faculty of Life Sciences: Food, Nutrition & Health, University of Bayreuth, 95326 Kulmbach, Germany.
  • Lampen A; Department Plant Quality and Food Security, Leibniz Institute of Vegetable and Ornamental Crops (IGZ), 14979 Grossbeeren, Germany.
  • Monien BH; Department of Food Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany.
  • Kleuser B; Department of Food Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany.
  • Glatt H; Department of Food Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany.
  • Schumacher F; Department of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany.
Chem Res Toxicol ; 36(11): 1753-1767, 2023 11 20.
Article em En | MEDLINE | ID: mdl-37875262
ABSTRACT
Methyleugenol (ME), found in numerous plants and spices, is a rodent carcinogen and is classified as "possibly carcinogenic to humans". The hypothesis of a carcinogenic risk for humans is supported by the observation of ME-derived DNA adducts in almost all human liver and lung samples examined. Therefore, a risk assessment of ME is needed. Unfortunately, biomarkers of exposure for epidemiological studies are not yet available. We hereby present the first detection of N-acetyl-l-cysteine conjugates (mercapturic acids) of ME in human urine samples after consumption of a popular ME-containing meal, pasta with basil pesto. We synthesized mercapturic acid conjugates of ME, identified the major product as N-acetyl-S-[3'-(3,4-dimethoxyphenyl)allyl]-l-cysteine (E-3'-MEMA), and developed methods for its extraction and LC-MS/MS quantification in human urine. For conducting an exposure study in humans, a basil cultivar with a suitable ME content was grown for the preparation of basil pesto. A defined meal containing 100 g of basil pesto, corresponding to 1.7 mg ME, was served to 12 participants, who collected the complete urine at defined time intervals for 48 h. Using d6-E-3'-MEMA as an internal standard for LC-MS/MS quantification, we were able to detect E-3'-MEMA in urine samples of all participants collected after the ME-containing meal. Excretion was maximal between 2 and 6 h after the meal and was completed within about 12 h (concentrations below the limit of detection). Excreted amounts were only between 1 and 85 ppm of the ME intake, indicating that the ultimate genotoxicant, 1'-sulfooxy-ME, is formed to a subordinate extent or is not efficiently detoxified by glutathione conjugation and subsequent conversion to mercapturic acids. Both explanations may apply cumulatively, with the ubiquitous detection of ME DNA adducts in human lung and liver specimens arguing against an extremely low formation of 1'-sulfooxy-ME. Taken together, we hereby present the first noninvasive human biomarker reflecting an internal exposure toward reactive ME species.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Acetilcisteína / Ocimum basilicum Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Acetilcisteína / Ocimum basilicum Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article