Furan induction of DNA cross-linking and strand breaks in turkey fetal liver in comparison to 1,3-propanediol

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• 作者：Alan M. Jeffrey^a ; Klaus D. Brunnemann^a ; Jian-Dong Duan^a ; Josef Schlatter^b ; Gary M. Williams^a ; ^{gary_williams@NYMC.EDU}
• 关键词：PDO ; 1 ; 3-propanediol ; DPXLs ; DNA&ndash ; protein cross-links ; DXL ; DNA cross-links ; DSB ; double strand breaks ; MDA ; malondialdehyde ; SSB ; single strand breaks ; TE ; Tris EDTA buffer
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：March-April, 2012
• 卷：50
• 期：3-4
• 页码：675-678
• 文件大小：283 K

摘要

Furan, a food contaminant formed by heating, is hepatocarcinogenic to rats and mice. Conflicting genotoxicity data exist on furan and its metabolite, cis-2-butene-1,4-dial and there are few data for the target organ, the liver. We assessed the abilities of furan and, as a positive control, 1,3-propanediol (PDO), to cause DNA damage in the livers of turkey fetuses in ovo using the alkaline comet assay. Single injections of furan (2-20 渭moles) into turkey eggs, at 23 days of incubation, when the liver is well developed, reduced the%DNA in the comet tail (%DNA-CT) in hepatocytes isolated from fetuses 24 h later indicating DNA cross links. Treatment of the hepatocytes with proteinase K, digest DNA-protein cross links (DPXLs), increased the%DNA-CT compared to the corresponding controls, indicating the presence of DNA single or double stand breaks (SB). PDO showed little toxicity and was used at high doses (up to 300 渭moles/egg), where it induced DPXLs at about 20 times the furan dose. Thus, furan produced dose proportional reductions in%DNA-CT in turkey liver fetal hepatocytes indicating the presence of DPXLs and, after proteinase K treatment, an increase in%DNA-CT, indicating the presence of DNA single and/or double SB.