2024-03-29T13:52:51Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/123482021-12-28T15:44:16Zcom_10261_5063com_10261_5col_10261_5066
Detection of DNA Adducts Derived from the Reactive Metabolite of Furan cis-2-Butene-1,4-dia
Byrns, Michael C.
Vu, Choua C.
Neidigh, Jonathan W.
Abad, José Luis
Jones, Roger A.
Peterson, Lisa A.
Furan
Toxic
Carcinogenic compound
Genotoxic
Nongenotoxic pathways
Cis-butene-1,4-dial
7 pages, 3 figures, 4 schemes.
Furan is a toxic and carcinogenic compound used in industry and commonly found in the environment. The mechanism of furan's carcinogenesis is not well-understood and may involve both genotoxic and nongenotoxic pathways. Furan undergoes oxidation by cytochrome P450 to cis-2-butene-1,4-dial, which is thought to mediate furan's toxic effects. Consistently, cis-2-butene-1,4-dial readily reacts with glutathione, amino acids, and nucleosides. To determine the importance of DNA alkylation in furan-induced carcinogenesis, we developed an assay for the detection of cis-2-butene-1,4-dial-derived DNA adducts. DNA samples were treated with O-benzyl-hydroxylamine, which reacts with the aldehyde functionality of the DNA adducts. Enzyme hydrolysates of these samples were then analyzed by capillary electrospray tandem mass spectrometry with selected reaction monitoring. The dCyd and dAdo adducts were detected in digests of DNA treated with nanomolar concentrations of cis-2-butene-1,4-dial. In addition, these adducts were present in DNA isolated from Ames assay strain TA104 treated with mutagenic concentrations of cis-2-butene-1,4-dial. These data support the hypothesis that cis-butene-1,4-dial is a genotoxic metabolite of furan. This method will allow us to explore the role of these adducts in furan-induced carcinogenesis.
Dr. Shana Sturla assisted with the 1H
NMR studies, and Dr. Peter Villalta and Brock Matter assisted in the MS studies. We thank Bob Carlson for his assistance in the preparation of this manuscript. This work was funded by NIH Grant ES-10577. M.C.B. was funded by a Doctoral
Dissertation Fellowship from the University of Minnesota Graduate School and NIH Training Grant ES-10956.
Peer reviewed
2009-04-16T11:17:21Z
2009-04-16T11:17:21Z
2006-02-28
artÃculo
http://purl.org/coar/resource_type/c_6501
Chemical Research in Toxicology 19(3): 414-420 (2006)
1520-5010
http://hdl.handle.net/10261/12348
10.1021/tx050302k
16544946
en
http://dx.doi.org/10.1021/tx050302k
none
19968 bytes
application/msword
American Chemical Society