A review of the genetic and related effects of 1,3-butadiene in rodents and humans

Jackson, Marcus; Stack, H.Frank; Rice, Jerry M.; Waters, Michael D.

doi:10.1016/s1383-5742(00)00056-9

Cited by 59 publications

(183 citation statements)

References 133 publications

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“…106-99-0) is a high production volume industrial chemical, largely produced through the processing of petroleum, and extensively used in the manufacture of synthetic rubber, polymers, and plastics (NTP, 2005). Exposure to BD occurs principally in the occupational settings of industrial facilities that produce and use this compound (Jackson et al, 2000;Anttinen-Klemetti et al, 2006). However, exposure to low levels of BD in urban air and in door settings do occur, since BD is also found in automobile exhaust and cigarette smoke (Adam et al, 2006;Grant et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Diepoxybutane activates the mitochondrial apoptotic pathway and mediates apoptosis in human lymphoblasts through oxidative stress

Yadavilli¹,

Martinez‐Ceballos²,

Snowden-Aikens³

et al. 2007

Toxicology in Vitro

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Diepoxybutane (DEB) is the most potent metabolite of the environmental chemical 1, 3-butadiene (BD), which is prevalent in petrochemical industrial areas. BD is a known mutagen and human carcinogen, and possesses multi-systems organ toxicity. We recently reported that DEB-induced cell death in TK6 lymphoblasts was due to the occurrence of apoptosis, and not necrosis. In this study, we investigated the molecular mechanisms responsible for DEB-induced apoptosis in these cells. Bax and Bak were found to be over-expressed and activated, and the mitochondrial trans-membrane potential was attenuated in cells undergoing DEB-induced apoptosis. Cytochrome c was depleted from the mitochondria of TK6 cells undergoing apoptosis, and was released into the cytosol in Jurkat-T lymphoblasts exposed to the same concentrations of DEB. Executioner caspase 3 was deduced to be activated by initiator caspase 9. DEB induced reactive oxygen species (ROS) formation, and the ROS scavenger N-acetyl-L-cysteine effectively blocked DEB-induced apoptosis in TK6 cells.Collectively, these results demonstrate that the mitochondrial apoptotic pathway is activated to mediate DEB-induced apoptosis in human TK6 lymphoblasts. These results further demonstrate that DEB-induced apoptosis is also mediated by the DEB-induced generation of ROS. This is the first report to examine the mechanism of DEB-induced apoptosis in human lymphoblasts.

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Section: Introductionmentioning

confidence: 99%

Diepoxybutane activates the mitochondrial apoptotic pathway and mediates apoptosis in human lymphoblasts through oxidative stress

Yadavilli¹,

Martinez‐Ceballos²,

Snowden-Aikens³

et al. 2007

Toxicology in Vitro

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“…Hydrolysis of BDO mediated by epoxide hydrolase forms 1,2-dihydroxy-3-butenes (29,32,33), which are metabolized by cytochrome P450 to hydroxymethylvinylketone (HMVK) (34). Either BDO 2 or the 1,2-dihydroxy-3-butenes may undergo cytochrome P450-mediated oxidation to form 1,2-dihydroxy-3,4-epoxybutanes (BDE) (29,32,35). Thus, proximate electrophiles arising from BD metabolism include BDO, BDO 2 , and BDE, and potentially, HMVK (36).…”

Section: Introductionmentioning

confidence: 99%

“…Either BDO 2 or the 1,2-dihydroxy-3-butenes may undergo cytochrome P450-mediated oxidation to form 1,2-dihydroxy-3,4-epoxybutanes (BDE) (29,32,35). Thus, proximate electrophiles arising from BD metabolism include BDO, BDO 2 , and BDE, and potentially, HMVK (36).…”

Section: Introductionmentioning

confidence: 99%

“…The genotoxicity is probably due to its potential to form DNA-DNA (43)(44)(45)(46) and DNA-protein cross-links (47,48), the latter having been observed in mice (49,50). Mice possess greater sensitivity to butadiene exposure than rats, and this is attributed to their efficient oxidation of BD to BDO 2 (51,52), presumably facilitating DNA cross-linking. Butadiene genotoxicity is further enhanced in knockout mice lacking a functional microsomal epoxide hydrolase gene (53).…”

Section: Introductionmentioning

confidence: 99%

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Structure of the 1,4-Bis(2‘-deoxyadenosin-N⁶-yl)-2S,3S-butanediol Intrastrand DNA Cross-Link Arising from Butadiene Diepoxide in the Human N-ras Codon 61 Sequence

Merritt

Nechev

et al. 2007

Chem. Res. Toxicol.

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The 1,4-bis(2′-deoxyadenosin-N 6 -yl)-2S,3S-butanediol intra-strand DNA cross-link arises from bisalkylation of tandem N 6 -dA sites in DNA by R,R-butadiene diepoxide (BDO 2 ). The oligodeoxynucleotide 5′-d(C 1 G 2 G 3 A 4 C 5 X 6 Y 7 G 8 A 9 A 10 G 11 )-3′·5′-d (C 12 T 13 T 14 C 15 T 16 T 17 G 18 T 19 C 20 C 21 G 22 )-3′ contains the BDO 2 cross-link between the second and third adenines of the codon 61 sequence (underlined) of the human N-ras protooncogene and is named the (S,S)-BD-(61-2,3) cross-link (X,Y = cross-linked adenines). NMR analysis reveals that the cross-link is oriented in the major groove of duplex DNA. Watson-Crick base pairing is perturbed at base pair X 6 ·T 17 , whereas base pairing is intact at base pair Y 7 ·T 16 . The cross-link appears to exist in two conformations, in rapid exchange on the NMR time scale. In the first conformation, the β-OH is predicted to form a hydrogen bond with T 16 O 4 , whereas in the second, the β-OH is predicted to form a hydrogen bond with T 17 O 4 . In contrast to the (R,R)-BD-(61-2,3) cross-link in the same sequence [Merritt, W.K., Nechev, L.V., Scholdberg, T.A., Dean, S.M., Kiehna, S.E., Chang, J.C., Harris, T.M., Harris, C.M., Lloyd, R.S., and Stone, M.P. (2005) Biochemistry 44, 10081-10092], the anti conformation of the two hydroxyl groups at C β and C γ with respect to the C β -C γ bond results in a decreased twist between base pairs X 6 ·T 17 and Y 7 ·T 16 , and an approximate 10° bending of the duplex. These conformational differences may account for the differential mutagenicity of the (S,S)-and (R,R)-BD-(61-2,3) cross-links, and suggest that stereochemistry plays a role in modulating biological responses to these cross-links [Kanuri, M., Nechev, L. V., Tamura, P. J., Harris, C. M., Harris, T. M., and Lloyd, R. S. (2002) Chem. Res. Toxicol. 15, 1572-1580.

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“…These BD N3-dU adducts were stable towards hydrolysis in DNA and as such, represent a potential source of mutagenesis, since this type of alkylation not only changes the base pairing of the parent nucleoside, but also has the potential to block DNA replication enzymes. Mutations at GC base pairs are critical events in BD mutagenicity as indicated by studies of mutations in lacI and lacZ mice and hprt mutational analyses in rodents and humans (reviewed in 39 ), thus suggesting modification of cytosine by BD metabolites and formation of the N3-dU adducts in vivo.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Mutagenesis of the Butadiene-Derived N3 2‘-Deoxyuridine Adducts

Fernandes

Hackfeld

Kozekov

et al. 2006

Chem. Res. Toxicol.

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Abstract1,3-Butadiene is a known carcinogen and mutagen that acts through a variety of metabolic intermediates that react with DNA, forming stable and unstable lesions on dG, dA, dC and dT. The N3 2′-deoxyuridine adducts are a highly stable, stereoisomeric mixture of adducts derived from the reaction of cytosine with the monoepoxide metabolite of butadiene, followed by spontaneous deamination. In this study, the phosphoramidites and subsequent oligodeoxynucleotides containing the N3 2′-deoxyuridine adducts have been constructed and characterized. Using a single-stranded shuttle vector DNA, the mutagenic potential of these adducts has been tested following replication in mammalian cells. Replication past the N3 2′-deoxyuridine adducts was found to be highly mutagenic with an overall mutation yield of ∼ 97%. The major mutations that were observed were C to T transitions and C to A transversions. In vitro, these adducts posed a complete block to both the Klenow fragment of Escherichia coli polymerase I and polymerase ε, while these lesions were significantly blocking to polymerase δ. These data suggested a possible involvement of bypass polymerases in the in vivo replication of these lesions. Overall these findings indicate that the N3 2′-deoxyuridine adducts are highly mutagenic lesions that may contribute to butadiene-mediated carcinogenesis.

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A review of the genetic and related effects of 1,3-butadiene in rodents and humans

Cited by 59 publications

References 133 publications

Diepoxybutane activates the mitochondrial apoptotic pathway and mediates apoptosis in human lymphoblasts through oxidative stress

Diepoxybutane activates the mitochondrial apoptotic pathway and mediates apoptosis in human lymphoblasts through oxidative stress

Structure of the 1,4-Bis(2‘-deoxyadenosin-N⁶-yl)-2S,3S-butanediol Intrastrand DNA Cross-Link Arising from Butadiene Diepoxide in the Human N-ras Codon 61 Sequence

Synthesis and Mutagenesis of the Butadiene-Derived N3 2‘-Deoxyuridine Adducts

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A review of the genetic and related effects of 1,3-butadiene in rodents and humans

Cited by 59 publications

References 133 publications

Diepoxybutane activates the mitochondrial apoptotic pathway and mediates apoptosis in human lymphoblasts through oxidative stress

Diepoxybutane activates the mitochondrial apoptotic pathway and mediates apoptosis in human lymphoblasts through oxidative stress

Structure of the 1,4-Bis(2‘-deoxyadenosin-N6-yl)-2S,3S-butanediol Intrastrand DNA Cross-Link Arising from Butadiene Diepoxide in the Human N-ras Codon 61 Sequence

Synthesis and Mutagenesis of the Butadiene-Derived N3 2‘-Deoxyuridine Adducts

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Structure of the 1,4-Bis(2‘-deoxyadenosin-N⁶-yl)-2S,3S-butanediol Intrastrand DNA Cross-Link Arising from Butadiene Diepoxide in the Human N-ras Codon 61 Sequence