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

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 μmoles) 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 μmoles/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.