Department of Toxicology, University of Würzburg, Würzburg, Germany.
Mol Nutr Food Res. 2012 Sep;56(9):1363-74. doi: 10.1002/mnfr.201200226. Epub 2012 Aug 3.
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.
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.
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.
糠醛是一种强有力的肝毒性和肝致癌物在啮齿动物。然而，糠醛遗传毒性的短期测试结果尚无定论。本研究的目的是评估糠醛与 DNA 发生共价结合的潜力，并评估糠醛在体内对大鼠的遗传毒性。
加速器质谱法用于测定[3,4-(14)C]-糠醛（0.1 和 2.0mg/kg bw）给药后大鼠 DNA 中的（14）C 含量。分析了糠醛处理 28 天的大鼠的 DNA 损伤、微核、染色体畸变和姐妹染色单体交换。
肝 DNA 中的（14）C 含量呈剂量依赖性显著增加，平均浓度分别为 7.9±3.5amol（14）C/μg DNA 和 153.3±100.2amol（14）C/μg DNA，分别相当于 0.1 和 2.0mg/kg bw 时 16.5±7.4 和 325.2±212.7 个加合物/10（9）个核苷酸。在外周血和骨髓细胞中没有发现糠醛的遗传毒性证据。然而，在大鼠脾细胞中观察到染色体畸变的发生率与剂量相关增加，并且在肝中观察到一些 DNA 损伤的迹象。总的来说，这项研究的结果表明，糠醛可能至少部分通过遗传毒性作用模式起作用。
