Furan-induced liver cell proliferation and apoptosis in female B6C3F1 mice

Fransson-Steen, Ronny; Goldsworthy, Thomas L.; Kedderis, Gregory L.; Maronpot, Robert R.

doi:10.1016/s0300-483x(97)03618-4

Cited by 57 publications

(53 citation statements)

References 30 publications

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“…Furan's toxic effects in model systems require metabolism (Burka et al, 1991;Carfagna et al, 1993;Kedderis et al, 1993;Parmar and Burka, 1993;Fransson-Steen et al, 1997;Mugford et al, 1997). The initial product of CYP-catalyzed oxidation of furan is cis-2-butene-1,4-dial (BDA; Fig.…”

Section: Introductionmentioning

confidence: 99%

Comparative Metabolism of Furan in Rodent and Human Cryopreserved Hepatocytes

et al. 2014

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Furan is a liver toxicant and carcinogen in rodents. Although humans are most likely exposed to furan through a variety of sources, the effect of furan exposure on human health is still unknown. In rodents, furan requires metabolism to exert its toxic effects. The initial product of the cytochrome P450 2E1-catalyzed oxidation is a reactive a,b-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA). BDA is toxic and mutagenic and consequently is considered responsible for the toxic effects of furan. The urinary metabolites of furan in rats are derived from the reaction of BDA with cellular nucleophiles, and precursors to these metabolites are detected in furan-exposed hepatocytes. Many of these precursors are 2-(S-glutathionyl) butanedial-amine cross-links in which the amines are amino acids and polyamines. Because these metabolites are derived from the reaction of BDA with cellular nucleophiles, their levels are a measure of the internal dose of this reactive metabolite. To compare the ability of human hepatocytes to convert furan to the same metabolites as rodent hepatocytes, furan was incubated with cryopreserved human and rodent hepatocytes. A semiquantitative liquid chromatography with tandem mass spectrometry assay was developed for a number of the previously characterized furan metabolites. Qualitative and semiquantitative analysis of the metabolites demonstrated that furan is metabolized in a similar manner in all three species. These results indicate that humans may be susceptible to the toxic effects of furan.

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Section: Introductionmentioning

confidence: 99%

Comparative Metabolism of Furan in Rodent and Human Cryopreserved Hepatocytes

et al. 2014

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“…[1][2][3] The mechanism of action involved in this toxicity rests on the cytochrome P450 mediated oxidation of the stable furan aromatic moiety into the reactive (Z)-2-butenedial, which is readily attacked by biological nucleophiles leading to a variety of deleterious adducts. [4][5][6] The study of its genotoxic effect and the underlying mechanism thereof continues to be an active area of interest and still needs to be completely understood.…”

Section: Introductionmentioning

confidence: 99%

Furan‐Oxidation‐Triggered Inducible DNA Cross‐Linking: Acyclic Versus Cyclic Furan‐Containing Building Blocks—On the Benefit of Restoring the Cyclic Sugar Backbone

Stevens

Claeys

Çatak

et al. 2011

Chemistry A European J

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Oligodeoxynucleotides incorporating a reactive functionality can cause irreversible cross-linking to the target sequence and have been widely studied for their potential in inhibition of gene expression or development of diagnostic probes for gene analysis. Reactive oligonucleotides further show potential in a supramolecular context for the construction of nanometer-sized DNA-based objects. Inspired by the cytochrome P450 catalyzed transformation of furan into a reactive enal species, we recently introduced a furan-oxidation-based methodology for cross-linking of nucleic acids. Previous experiments using a simple acyclic building block equipped with a furan moiety for incorporation into oligodeoxynucleotides have shown that cross-linking occurs in a very fast and efficient way and that substantial amounts of stable, site-selectively cross-linked species can be isolated. Given the destabilization of duplexes observed upon introduction of the initially designed furan-modified building block into DNA duplexes, we explore here the potential benefits of two new building blocks featuring an extended aromatic system and a restored cyclic backbone. Thorough experimental analysis of cross-linking reactions in a series of contexts, combined with theoretical calculations, permit structural characterization of the formed species and allow assessment of the origin of the enhanced cross-link selectivity. Our experiments clearly show that the modular nature of the furan-modified building blocks used in the current cross-linking strategy allow for fine tuning of both yield and selectivity of the interstrand cross-linking reaction.

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“…Neuere Untersuchungen zeigen allerdings, dass Entkoppler der mitochondrialen Atmungskette weniger über den beschriebenen Calcium-Mechanismus, als über die Öffnung der mitochondrialen Transitionsporen eine Apoptose auslösen (Klöhn et al 2003). Erst bei höheren Dosierungen (ab 8 mg/kg KG und Tag bei weiblichen B6C3F1-Mäusen) entstehen durch unspezifische Reaktionen Nekrosen (Fransson-Steen et al 1997). Bei der Exposition isolierter Rattenhepatozyten gegen Furan wurde eine irreversible konzentrations-und zeitabhängige Abnahme von ATP in den Zellen nachgewiesen.…”

Section: Wirkungsmechanismusunclassified

Furan [MAK Value Documentation in German language, 2006]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 40. Lieferung, Ausgabe 2006 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Toxikokinetik und Metabolismus Aufnahme, Verteilung, Ausscheidung Metabolismus Erfahrungen beim Menschen Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Sonstige Wirkungen Bewertung

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Furan-induced liver cell proliferation and apoptosis in female B6C3F1 mice

Cited by 57 publications

References 30 publications

Comparative Metabolism of Furan in Rodent and Human Cryopreserved Hepatocytes

Comparative Metabolism of Furan in Rodent and Human Cryopreserved Hepatocytes

Furan‐Oxidation‐Triggered Inducible DNA Cross‐Linking: Acyclic Versus Cyclic Furan‐Containing Building Blocks—On the Benefit of Restoring the Cyclic Sugar Backbone

Furan [MAK Value Documentation in German language, 2006]

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