Electrophilic intermediates produced by bioactivation of furan

被引：50
作者：
Peterson, Lisa A.
机构：
[1] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN 55455 USA
来源：
DRUG METABOLISM REVIEWS | 2006年 / 38卷 / 04期
关键词：
furan; carcinogenesis; toxicity; metabolism; glutathione conjugates; stable isotope methods; alpha; beta-unsaturated aldehyde;
D O I：
10.1080/03602530600959417
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The industrial and environmental chemical, furan, is a liver toxicant and carcinogen in laboratory animals. It has been classified as a possible human carcinogen. The mechanism of tumor induction is unknown. However, toxicity is initiated by cytochrome P450 catalyzed oxidation of furan to an alpha,beta-unsaturated dialdehyde, cis-2-butene-1,4-dial This metabolite reacts readily with protein and DNA nucleophiles and is a bacterial mutagen in Ames assay strain TA104. Metabolism studies indicate that this reactive metabolite is formed in vivo. It is also an intermediate leading to other metabolites whose role in furan-derived toxicities has yet to be explored.
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收藏
页码：615 / 626
页数：12
相关论文
共 38 条
[1]   OXIDATION OF FURANS WITH DIMETHYLDIOXIRANE - INTERCEPTION OF MALEALDEHYDE AND RELATED ALDEHYDES VIA WITTIG REACTIONS [J].
ADGER, BJ ;
BARRETT, C ;
BRENNAN, J ;
MCGUIGAN, P ;
MCKERVEY, MA ;
TARBIT, B .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1993, (15) :1220-1222
[2]  
BREUSCH FL, 1952, H-S Z PHYSIOL CHEM, V291, P60
[3]   DISPOSITION OF [C-14] FURAN IN THE MALE F344 RAT [J].
BURKA, LT ;
WASHBURN, KD ;
IRWIN, RD .
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, 1991, 34 (02) :245-257
[4]   Detection of DNA adducts derived from the reactive metabolite of furan, cis-2-butene-1,4-dial [J].
Byrns, MC ;
Vu, CC ;
Neidigh, JW ;
Abad, JL ;
Jones, RA ;
Peterson, LA .
CHEMICAL RESEARCH IN TOXICOLOGY, 2006, 19 (03) :414-420
[5]   The formation of substituted 1,N6-etheno-2′-deoxyadenosine and 1,N2-etheno-2′-deoxyguanosine adducts by cis-2-butene-1,4-dial, a reactive metabolite of furan [J].
Byrns, MC ;
Vu, CC ;
Peterson, LA .
CHEMICAL RESEARCH IN TOXICOLOGY, 2004, 17 (12) :1607-1613
[6]   Characterization of nucleoside adducts of cis-2-butene-1,4-dial, a reactive metabolite of furan [J].
Byrns, MC ;
Predecki, DP ;
Peterson, LA .
CHEMICAL RESEARCH IN TOXICOLOGY, 2002, 15 (03) :373-379
[7]   EFFECTS OF EXPOSURE TO SOLVENTS CAUSED BY AIR-POLLUTION WITH SPECIAL REFERENCE TO CCL4 AND ITS DISTRIBUTION IN AIR [J].
CAPURRO, PU .
CLINICAL TOXICOLOGY, 1973, 6 (01) :109-124
[8]   FURAN-INDUCED CYTOLETHALITY IN ISOLATED RAT HEPATOCYTES - CORRESPONDENCE WITH IN-VIVO DOSIMETRY [J].
CARFAGNA, MA ;
HELD, SD ;
KEDDERIS, GL .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1993, 123 (02) :265-273
[9]   Characterization of amino acid on glutathione adducts of cis-2-butene-1,4-dial, a reactive metabolite of furan [J].
Chen, LJ ;
Hecht, SS ;
Peterson, LA .
CHEMICAL RESEARCH IN TOXICOLOGY, 1997, 10 (08) :866-874
[10]   IDENTIFICATION OF CIS-2-BUTENE-1,4-DIAL AS A MICROSOMAL METABOLITE OF FURAN [J].
CHEN, LJ ;
HECHT, SS ;
PETERSON, LA .
CHEMICAL RESEARCH IN TOXICOLOGY, 1995, 8 (07) :903-906
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