TY - JOUR
T1 - Furan carcinogenicity
T2 - DNA binding and genotoxicity of furan in rats in vivo
AU - Neuwirth, Carolin
AU - Mosesso, Pasquale
AU - Pepe, Gaetano
AU - Fiore, Mario
AU - Malfatti, Mike
AU - Turteltaub, Ken W
AU - Dekant, Wolfgang
AU - Mally, Angela
PY - 2012/9
Y1 - 2012/9
N2 - 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 14C-content in DNA following administration of [3,4-14C]-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 14C-content in liver DNA was significantly increased in a dose-dependent manner, with mean concentrations of 7.9 ± 3.5 amol 14C/μg DNA and 153.3 ± 100.2 amol 14C/μg DNA, corresponding to 16.5 ± 7.4 and 325.2 ± 212.7 adducts/109 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.
AB - 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 14C-content in DNA following administration of [3,4-14C]-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 14C-content in liver DNA was significantly increased in a dose-dependent manner, with mean concentrations of 7.9 ± 3.5 amol 14C/μg DNA and 153.3 ± 100.2 amol 14C/μg DNA, corresponding to 16.5 ± 7.4 and 325.2 ± 212.7 adducts/109 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.
KW - Carcinogenicity
KW - DNA adducts
KW - Furan
KW - Genotoxicity
KW - Liver
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U2 - 10.1002/mnfr.201200226
DO - 10.1002/mnfr.201200226
M3 - Article
C2 - 22865590
AN - SCOPUS:84865782211
VL - 56
SP - 1363
EP - 1374
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
SN - 1613-4125
IS - 9
ER -