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.