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Furan carcinogenicity: DNA binding and genotoxicity of furan in rats in vivo
Author(s) -
Neuwirth Carolin,
Mosesso Pasquale,
Pepe Gaetano,
Fiore Mario,
Malfatti Mike,
Turteltaub Ken,
Dekant Wolfgang,
Mally Angela
Publication year - 2012
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200226
Subject(s) - genotoxicity , furan , carcinogen , dna damage , chemistry , micronucleus test , dna , in vivo , dna adduct , sister chromatids , microbiology and biotechnology , biochemistry , pharmacology , biology , toxicity , genetics , organic chemistry , gene , chromosome
Scope 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. Materials and 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. Conclusion 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.