title: Protective effects of coffee against oxidative stress induced by the tobacco carcinogen benzo[α]pyrene.
abstract: Coffee consumption has been epidemiologically associated with a lower risk for liver cirrhosis and cancer. UDP-glucuronosyltransferases (UGT1A) catalyze the detoxification of reactive metabolites thereby acting as indirect antioxidants. Aim of the study was to examine UGT1A regulation in response to Benzo[α]pyrene (BaP) to elucidate the potentially protective effects of coffee on BaP-induced oxidative stress and toxicity.
  
  
  
  In cell culture (HepG2, KYSE70 cells) and in htgUGT1A-WT mice, UGT1A transcription was activated by BaP, while it was reduced or absent htgUGT1A-SNP (containing 10 commonly occurring UGT1A-SNPs) mice. siRNA-mediated knockdown identified aryl hydrocarbon receptor (AhR) and nuclear factor erythroid2-related factor-2 (Nrf2) as mediators of BaP-induced UGT1A upregulation. Exposure to coffee led to a reduction of BaP-induced production of reactive oxygen species in vitro and in htgUGT1A-WT and -SNP mice. After UGT1A silencing by UGT1A-specific siRNA in cell culture, the coffee-mediated reduction of ROS production was significantly impaired compared to UGT1A expressing cells.
  
  
  
  A common UGT1A haplotype, prevalent in 9% (homozygous) of the White population, significantly impairs the expression of UGT1A enzymes in response to the putative tobacco carcinogen BaP and is likely to represent a significant risk factor for reduced detoxification and increased genotoxicity. Coffee was demonstrated to inhibit BaP-induced production of oxidative stress by UGT1A activation, and is therefore an attractive candidate for chemoprotection in risk groups for HCC or other tumors.
authors.affiliation: Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany. Electronic address: sandra.kalthoff@ukb.uni-bonn.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kalthoff
authors.affiliation: Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany. Electronic address: steffen.landerer@ukb.uni-bonn.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Landerer
authors.affiliation: Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany. Electronic address: julia.reich@ukb.uni-bonn.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Reich
authors.affiliation: Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany. Electronic address: christian.strassburg@ukb.uni-bonn.de.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Strassburg
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001580:Benzopyrenes / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000178:diet therapy / Q000453:epidemiology* / Q000235:genetics; D040503:Coffea; D003069:Coffee / Q000378:metabolism*; D004435:Eating; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008103:Liver Cirrhosis / Q000178:diet therapy / Q000453:epidemiology* / Q000235:genetics; D008113:Liver Neoplasms / Q000178:diet therapy / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D012306:Risk; D000073869:Tobacco Smoking / Q000009:adverse effects; D044465:White People; D000099148:UGT1A1 Enzyme
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001580:Benzopyrenes; D003069:Coffee; D014453:Glucuronosyltransferase; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; D000099148:UGT1A1 Enzyme; C111235:AHR protein, human
keywords: BaP; Coffee; Glucuronidation; Oxidative stress