Abstract
Furan is a volatile compound that is formed in foods during thermal processing. It is classified as a possible human carcinogen by international authorities based on sufficient evidence of carcinogenicity from studies in experimental animals. Although a vast number of studies both in vitro and in vivo have been performed to investigate furan genotoxicity, the results are inconsistent, and its carcinogenic mode of action remains to be clarified. Here, we address the mutagenic and clastogenic activity of furan and its prime reactive metabolite cis-2 butene-1,4-dial (BDA) in mammalian cells in culture and in mouse animal models in a search for DNA lesions responsible of these effects. To this aim, Fanconi anemia-derived human cell lines defective in the repair of DNA inter-strand crosslinks (ICLs) and Ogg1−/− mice defective in the removal of 8-hydroxyguanine from DNA, were used. We show that both furan and BDA present a weak (if any) mutagenic activity but are clear inducers of clastogenic damage. ICLs are strongly indicated as key lesions for chromosomal damage whereas oxidized base lesions are unlikely to play a critical role.
Highlights
The above described data raise the following questions (i) what is the role of CYP1E1 metabolism in the induction of clastogenic effects, and (ii) what are the DNA lesions involved? To answer these questions, we investigated the ability of furan to induce chromosomal aberrations in cell lines defective in the repair of DNA inter-strand crosslinks (ICLs) both in the absence and in the presence of S9 fractions
At first the mutational activity of furan and BDA was investigated in mammalian cell lines
This problem together with conditions of cell exposure in closed systems may underlie the controversial data reported in the literature using the same mutation assays [9,10]
Summary
Furan is a volatile organic chemical that is formed during the processing or cooking of many common foods. It is found in tobacco smoke and is used as a synthetic intermediate in the production of pesticides, stabilizers, and solvent for resins and pharmaceuticals. The widespread human exposure to furan through the diet is a public health concern because of its hepatotoxicity and carcinogenicity in rats and mice [1,2,3,4]. Oral exposure to furan caused tumors at several different tissue sites in mice and rats.
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