title: Furan carcinogenicity: DNA binding and genotoxicity of furan in rats in vivo.
abstract: METHODS
  Furan is a potent hepatotoxicant and liver carcinogen in rodents. However, short-term tests for genotoxicity of furan are inconclusive. The aim of this study was to assess the potential of furan to covalently bind to DNA, and to assess furan genotoxicity in rats in vivo.
  
  
  METHODS
  Accelerator mass spectrometry was used to determine the (14) C-content in DNA following administration of [3,4-(14) C]-furan (0.1 and 2.0 mg/kg bw) to F344 rats. DNA damage, micronuclei, chromosomal aberrations, and sister chromatid exchanges were analyzed in F344 rats treated with furan for up to 28 days.
  
  
  CONCLUSIONS
  The (14) C-content in liver DNA was significantly increased in a dose-dependent manner, with mean concentrations of 7.9 ± 3.5 amol (14) C/μg DNA and 153.3 ± 100.2 amol (14) C/μg DNA, corresponding to 16.5 ± 7.4 and 325.2 ± 212.7 adducts/10(9)  nucleotides at 0.1 and 2.0 mg/kg bw, respectively. There was no evidence for genotoxicity of furan in peripheral blood and bone marrow cells. However, a dose-related increase in the incidence of chromosomal aberrations in rat splenocytes and some indication of DNA damage in liver were observed. Collectively, results from this study indicate that furan may operate-at least in part-by a genotoxic mode of action.
authors.affiliation: Department of Toxicology, University of Würzburg, Würzburg, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Neuwirth
authors.forename: Pasquale
authors.initials: P
authors.lastname: Mosesso
authors.forename: Gaetano
authors.initials: G
authors.lastname: Pepe
authors.forename: Mario
authors.initials: M
authors.lastname: Fiore
authors.forename: Mike
authors.initials: M
authors.lastname: Malfatti
authors.forename: Ken
authors.initials: K
authors.lastname: Turteltaub
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dekant
authors.forename: Angela
authors.initials: A
authors.lastname: Mally
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000187:drug effects*; D005663:Furans / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests; D009369:Neoplasms / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D012854:Sister Chromatid Exchange / Q000187:drug effects
chemical_list: D002273:Carcinogens; D004268:DNA-Binding Proteins; D005663:Furans; C039281:furan