title: Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid.
abstract: Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (γ-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor Garc&#237;a Gonz&#225;lez 2, 41012 Seville, Spain. eburgos1@us.es.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Burgos-Morón
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor Garc&#237;a Gonz&#225;lez 2, 41012 Seville, Spain. jose.calderon@cabimer.es.|Department of Molecular Biology, Centro Andaluz de Biolog&#237;a Molecular y Medicina Regenerativa, University of Seville, Avda. Americo Vespucio s/n., 41092 Seville, Spain. jose.calderon@cabimer.es.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Calderón-Montaño
authors.affiliation: Department of Cell Biology, Faculty of Biology, University of Seville, Avda. Reina Mercedes s/n., 41012 Seville, Spain. morta2@us.es.
authors.forename: Manuel Luis
authors.initials: ML
authors.lastname: Orta
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor Garc&#237;a Gonz&#225;lez 2, 41012 Seville, Spain. eguillen@us.es.
authors.forename: Emilio
authors.initials: E
authors.lastname: Guillén-Mancina
authors.affiliation: Department of Cell Biology, Faculty of Biology, University of Seville, Avda. Reina Mercedes s/n., 41012 Seville, Spain. smateos@us.es.
authors.forename: Santiago
authors.initials: S
authors.lastname: Mateos
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor Garc&#237;a Gonz&#225;lez 2, 41012 Seville, Spain. mlopezlazaro@us.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Lázaro
mesh_terms: D002109:Caffeic Acids / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003069:Coffee / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000172:deficiency* / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D000071857:Tumor Suppressor p53-Binding Protein 1 / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D003069:Coffee; C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; C468783:H2AX protein, human; D006657:Histones; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; C040048:caffeic acid
keywords: DNA damage; FANCD2; Fanconi anemia; caffeic acid; cancer; carcinogenesis; coffee