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1. Acute catabolism of leukocyte lipid bodies: Characterization of a nordihydroguaiaretic acid (NDGA)-induced proteasomal-dependent model.

Author

de Lira MN, Bolini L, Amorim NRT, Silva-Souza HA, Diaz BL, Canetti C, Persechini PM, and Bandeira-Melo C

Subjects
Animals, Eosinophils drug effects, Eosinophils metabolism, Leukocytes metabolism, Lipid Droplets metabolism, Macrophages drug effects, Macrophages metabolism, Mice, Neutrophils drug effects, Neutrophils metabolism, Proteasome Endopeptidase Complex metabolism, Leukocytes drug effects, Lipid Droplets drug effects, Lipoxygenase Inhibitors pharmacology, Masoprocol pharmacology, Proteasome Endopeptidase Complex drug effects
Abstract

Cytoplasmic availability of leukocyte lipid bodies is controlled by a highly regulated cycle of opposing biogenesis- and catabolism-related events. While leukocyte biogenic machinery is well-characterized, lipid body catabolic mechanisms are yet mostly unknown. Here, we demonstrated that nordihydroguaiaretic acid (NDGA) very rapidly decreases the numbers of pre-formed lipid bodies within lipid body-enriched cytoplasm of mouse leukocytes - macrophages, neutrophils and eosinophils. NDGA mechanisms driving leukocyte lipid body disappearance were not related to loss of cell viability, 5-lipoxygenase inhibition, ATP autocrine/paracrine activity, or biogenesis inhibition. Proteasomal-dependent breakdown of lipid bodies appears to control NDGA-driven leukocyte lipid body reduction, since it was Bortezomib-sensitive in macrophages, neutrophils and eosinophils. Our findings unveil an acute NDGA-triggered lipid body catabolic event - a novel experimental model for the still neglected research area on leukocyte lipid body catabolism, additionally favoring further insights on proteasomal contribution to lipid body breakdown., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Published
2021
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2. Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study

Author

Carmen Martinez, Petra H.M. Peeters, Merethe Kumle, Paolo Vineis, Armelle Munnia, Seymour Garte, Bas Bueno-de-Mesquita, Emmanuelle Gormally, Ole Raaschou-Nielsen, Antonio Agudo, Giuseppe Matullo, Bengt Järvholm, Françoise Clavel-Chapelon, José Ramón Quirós, Göran Berglund, Marco Peluso, Alison M. Dunning, Rosario Tumino, Alessandro Colombi, Salvatore Panico, Timothy J. Key, Luisa Airoldi, Elio Riboli, S Bingham, Fabrizio Veglia, Rudolf Kaaks, Antonia Trichopoulou, Aurelio Barricarte, Vittorio Krogh, Christian Malaveille, Nicholas E. Day, Kim Overvad, Rodolfo Saracci, Herman Autrup, María José Tormo, Domenico Palli, J. Linseisen, Heiner Boeing, Miren Dorronsoro, Faculteit Medische Wetenschappen/UMCG, Peluso, M, Airoldi, L, Munnia, A, Colombi, A, Veglia, F, Autrup, H, Dunning, A, Garte, S, Gormally, E, Malaveille, C, Matullo, G, Overvad, K, Raaschou Nielsen, O, Clavel Chapelon, F, Linseisen, J, Boeing, H, Trichopoulou, A, Palli, D, Krogh, V, Tumino, R, Panico, Salvatore, Bueno De Mesquita, Bh, Peeters, Ph, Kumle, M, Agudo, A, Martinez, C, Dorronsoro, M, Barricarte, A, Tormo, Mj, Quiros, Jr, Berglund, G, Jarvholm, B, Day, Ne, Key, Tj, Saracci, R, Kaaks, R, Riboli, E, Bingham, S, Vineis, P., [Peluso,M, Munnia, A] Cancer Risk Factor Branch, Analytical and Biomolecular Cytology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy. [Airoldi,L, Colombi,A] Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. [Veglia, F, Matullo,G] ISI Foundation, Turin, Italy. [Autrup,H] Department of Environmental and Occupational Medicine, Aarhus, Denmark. [Dunning, A] Department of Oncology, University of Cambridge, Cambridge, UK. [Garte,S] Genetics Research Institute, Milan, Italy. [Gormally,E, Malaveille,C] International Agency for Research on Cancer, Lyon, France. [Overhad,K] Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Raaschou-Nielsen,O] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Clavel-Chapelon,F] INSERM (Institut National de la Sante´ et de la Recherche Me´dicale), ERI 20, EA 4045, and Institut Gustave Roussy, Villejuif, F-94805, France. [Linseisen,J] Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, German. [Boeing,H] German Institute of Human Nutrition, Potsdam-Rehbu¨cke, Germany. [Trichopoulou,A] Department of Hygiene and Epidemiology, Medical School, University of Athens, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Cancer Prevention Tuscany Region, Florence, Italy. [Krogh,V] Department of Epidemiology, National Cancer Institute, Milan, Italy. [Tumino,R] Cancer Registry, Azienda Ospedaliera ‘Civile MP Arezzo’, Ragusa, Ital. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Universita` Federico II, Naples, Italy. [Bueno-De-Mesquita,BH] Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherland. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. [Kumle,M] Institute of Community Medicine, University of Tromso, Tromso, Norway. [Agudo,A] Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain. [Martinez,C] Andalusian School of Public Health, Granada, Spain. [Dorronsoro,M] Department of Public Health of Guipuzkoa, San Sebastian, Spain. [Barricarte,A] Public Health Institute, Navarra, Spain. [Tormo,MJ] Epidemiology Department, Murcia Health Council, Murcia, Spain. Quiros, JR] Direccio´n General de Salud Pu´blica, Consejerı´a de Salud y Servicios Sanitarios Asturias, Oviedo, Spain. [Berglund,G] Malmo¨ Diet and Cancer Study, Lund University, Malmo¨, Sweden. [Jarvholm,G] Department of Nutritional Research, University of Umea˚, Umea˚ , Sweden. [Day,ND, Bingham,S] MRC Dunn Human Nutrition Unit, Cambridge University, UK. [Key,TJ].Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, UK. [Saracci,R] IFC National Research Council, Pisa, Italy. [Kaas,R] Division of Epidemiology, DKFZ Heidelberg, Germany. [Riboli,E] Imperial College London, London, UK. [Vineis,P] University of Turin, Turin, Italy. Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 1PG, UK, This paper was made possible by a grant of the European Community (5th Framework Programme) to P. V. (grant QLK4–CT–1999–00 927) and a grant of the Compagnia di San Paolo to the ISI Foundation. All authors are independent from funders. Mortality data for the Netherlands were obtained from Statistics Netherlands. Also, the work described in the paper was carried out with the financial support of: Europe Against Cancer Program of the European Commission (SANCO), ISCIII, Red de Centros RCESP, C03/09, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Dutch Ministry of Public Health, Welfare and Sports, World Cancer Research Fund, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Ska°ne, Sweden, Norwegian Cancer Society, and Research Council of Norway.

Subjects
Dietary Fiber, Male, Aflatoxin, Erythrocytes, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Hemoglobins [Medical Subject Headings], medicine.medical_treatment, air pollution, RESISTANT STARCH, Medicine (miscellaneous), GUIDELINES, Carcinógenos, Body Mass Index, COLORECTAL-CANCER, Food group, chemistry.chemical_compound, Hemoglobins, Vegetables, Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants::Air Pollutants [Medical Subject Headings], Leukocytes, Aductos de ADN, Nutritional Physiological Phenomena, Food science, Prospective Studies, RISK, DNA adducts, Haemoglobin adducts, Non-smokers, Fibre intake, Air pollution, Publication Characteristics::Study Characteristics::Multicenter Study [Medical Subject Headings], Air Pollutants, Nutrition and Dietetics, Chemistry, Technology, Industry, Agriculture::Food and Beverages::Food::Dietary Fiber [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Noxae::Carcinogens [Medical Subject Headings], COLON-CANCER, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage::DNA Adducts [Medical Subject Headings], Fabaceae, Middle Aged, fibre intake, European Prospective Investigation into Cancer and Nutrition, Europe, Biochemistry, 4-Aminobiphenyl, Colonic Neoplasms, Hemoglobinas, Female, SMOKERS, Alcohol Drinking, BLADDER-CANCER, European Prospective Investigation into Cancer and Nutrition (EPIC), haemoglobin adducts, non-smokers, RATS, POLYCYCLIC AROMATIC-HYDROCARBONS, Ozone, LUNG-CANCER, DNA adduct, medicine, Humans, Contaminantes del aire, ddc:610, Carcinogen, Aged, Estudio multicéntrico, Vitamin E, Fruit, Multivariate Analysis, Fibras en la dieta, Carcinogens, Biomarkers, Food contaminant
Abstract

Udgivelsesdato: 2008-Feb-14 In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0.02), vitamin E (P = 0.04) and alcohol (P = 0.03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0.03, 0.04, and 0.03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.

Published
2008