title: Aristolochic acid exposure in Romania and implications for renal cell carcinoma.
abstract: BACKGROUND
  Aristolochic acid (AA) is a nephrotoxicant associated with AA nephropathy (AAN) and upper urothelial tract cancer (UUTC). Whole-genome sequences of 14 Romanian cases of renal cell carcinoma (RCC) recently exhibited mutational signatures consistent with AA exposure, although RCC had not been previously linked with AAN and AA exposure was previously reported only in localised rural areas.
  
  
  METHODS
  We performed mass spectrometric measurements of the aristolactam (AL) DNA adduct 7-(deoxyadenosin-N(6)-yl) aristolactam I (dA-AL-I) in nontumour renal tissues of the 14 Romanian RCC cases and 15 cases from 3 other countries.
  
  
  RESULTS
  We detected dA-AL-I in the 14 Romanian cases at levels ranging from 0.7 to 27 adducts per 10(8) DNA bases, in line with levels reported in Asian and Balkan populations exposed through herbal remedies or food contamination. The 15 cases from other countries were negative.
  
  
  CONCLUSIONS
  Although the source of exposure is uncertain and likely different in AAN regions than elsewhere, our results demonstrate that AA exposure in Romania exists outside localised AAN regions and provide further evidence implicating AA in RCC.
authors.affiliation: Masonic Cancer Center and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Turesky
authors.affiliation: Masonic Cancer Center and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Yun
authors.affiliation: International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, Lyon 69008, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: National Institute of Public Health, 1-3 Doctor Leonte Anastasievici, Sector 5, Bucharest 050463, Romania.
authors.forename: Dana
authors.initials: D
authors.lastname: Mates
authors.affiliation: Carol Davila University of Medicine and Pharmacy, Th. Burghele Hospital, 20 Panduri Street, Bucharest 050659, Romania.
authors.forename: Viorel
authors.initials: V
authors.lastname: Jinga
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Cancer Research Building, St James's University Hospital, Leeds LS9 7TF, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Harnden
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Cancer Research Building, St James's University Hospital, Leeds LS9 7TF, UK.
authors.forename: Rosamonde E
authors.initials: RE
authors.lastname: Banks
authors.affiliation: Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain, 27 Rue Juliette Dodu, Paris 75010, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Blanche
authors.affiliation: Centre National de Genotypage, Institut de Genomique, Centre de l'Energie Atomique et aux Energies Alternatives, 2 Rue Gaston Cremieux, Evry 91000, France.
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Bihoreau
authors.affiliation: International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, Lyon 69008, France.
authors.forename: Priscilia
authors.initials: P
authors.lastname: Chopard
authors.affiliation: McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, Quebec H3A 0G1, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Letourneau
authors.affiliation: McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, Quebec H3A 0G1, Canada.
authors.forename: G Mark
authors.initials: GM
authors.lastname: Lathrop
authors.affiliation: International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, Lyon 69008, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Scelo
mesh_terms: D034341:Aristolochic Acids / Q000032:analysis / Q000633:toxicity*; D002292:Carcinoma, Renal Cell / Q000139:chemically induced* / Q000235:genetics; D003839:Deoxyadenosines / Q000032:analysis; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000235:genetics; D009154:Mutation; D012383:Romania; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D034341:Aristolochic Acids; D003839:Deoxyadenosines; C077580:7-(deoxyadenosin-N(6)-yl)aristolactam I; C000228:aristolochic acid I