Metabolism of 1,3-butadiene: species differences

Henderson, Rogene F.; Thornton‐Manning, Janice R.; Bechtold, William E.; Dahl, Alan R.

doi:10.1016/0300-483x(96)03422-1

Cited by 61 publications

(76 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 1,2;3,4-diepoxybutane-specific adducts exhibit the greatest species difference, whereas 3,4-epoxy-1,2-butanediol adducts show the least difference. Previous studies measuring 1,2-epoxy-3-butene and 1,2; 3,4-diepoxybutane concentrations in blood also demonstrated that mice were more efficient than rats in 1,2;3,4-diepoxybutane formation when exposed to 62.5 ppm 1,3-butadiene (21).…”

Section: Resultsmentioning

confidence: 86%

Analysis of Diepoxide-Specific Cyclic N -Terminal Globin Adducts in Mice and Rats after Inhalation Exposure to 1,3-Butadiene

et al. 2004

View full text Add to dashboard Cite

Abstract1,3-Butadiene is an important industrial chemical used in the production of synthetic rubber and is also found in gasoline and combustion products. It is a multispecies, multisite carcinogen in rodents, with mice being the most sensitive species. 1,3-Butadiene is metabolized to several epoxides that form DNA and protein adducts. Previous analysis of 1,2,3-trihydroxybutyl-valine globin adducts suggested that most adducts resulted from 3-butene-1,2-diol metabolism to 3,4-epoxy-1,2-butanediol, rather than from 1,2;3,4-diepoxybutane. To specifically examine metabolism of 1,3-butadiene to 1,2;3,4-diepoxybutane, the formation of the 1,2;3,4-diepoxybutane-specific adduct N,N-(2,3-dihydroxy-1,4-butadiyl)-valine was evaluated in mice treated with 3, 62.5, or 1250 ppm 1,3-butadiene for 10 days and rats exposed to 3 or 62.5 ppm 1,3-butadiene for 10 days, or to 1000 ppm 1,3-butadiene for 90 days, using a newly developed immunoaffinity liquid chromatography tandem mass spectrometry assay. In addition, 2-hydroxy-3-butenyl-valine and 1,2,3-trihydroxybutylvaline adducts were determined. The analyses of several adducts derived from 1,3-butadiene metabolites provided new insight into species and exposure differences in 1,3-butadiene metabolism. Mice formed much higher amounts of N,N-(2,3-dihydroxy-1,4-butadiyl)-valine than rats. The formation of 2-hydroxy-3-butenyl-valine and N,N-(2,3-dihydroxy-1,4-butadiyl)-valine was similar in mice exposed to 3 or 62.5 ppm 1,3-butadiene, whereas 2-hydroxy-3-butenyl-valine was 3-fold higher at 1250 ppm. In both species, 1,2,3-trihydroxybutyl-valine adducts were much higher than 2-hydroxy-3-butenyl-valine and N,N-(2,3-dihydroxy-1,4-butadiyl)-valine. Together, these data show that 1,3-butadiene is primarily metabolized via the 3-butene-1,2-diol pathway, but that mice are much more efficient at forming 1,2;3,4-diepoxybutane than rats, particularly at low exposures. This assay should also be readily adaptable to molecular epidemiology studies on 1,3-butadiene-exposed workers

show abstract

Section: Resultsmentioning

confidence: 86%

Analysis of Diepoxide-Specific Cyclic N -Terminal Globin Adducts in Mice and Rats after Inhalation Exposure to 1,3-Butadiene

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Partially and fully TMSE-protected cross-linked products were combined, and after lyophilization the TMSE-protecting groups were removed by treatment with aqueous acetic acid (pH 3) for 2 h at room temperature; the product coeluted with fully deprotected cross-link 3b. The reaction mixture was then neutralized, combined with 3b, lyophilized, and repurified by HPLC on a C18 column (250 ϫ 10 mm, YMC ODS-AQ) with the following gradient: (A) 0.1 M ammonium formate and (B) CH 3 CN, 3-13% B over 25 min, 13-90% B over 2 min, hold for 2 min, and then to 2 The abbreviations used are: TMSE, 2-fluoro-O 9. Capillary gel electrophoresis and enzymatic digestion to the constituent nucleosides were also used to confirm the purity and composition of 3a and 3b.…”

Section: Ss)-butadiene Cross-link (3b)-for Synthesis Of This Cross-lmentioning

confidence: 99%

“…Enzymatic digestion showed the constituent nucleosides in the expected ratios (3dC, 2T, 1dA, and 1 bisnucleoside). To rigorously minimize the possibility of contaminants that could alter the mutagenic spectrum, the ras 12 2 8-mers were extensively purified and analyzed. Each 8-mer was labeled by T4 DNA kinase, using [␥-32 P]ATP, and the final purity was determined by separating the labeled 8-mers on a denaturing polyacrylamide gel and examining for the presence of any contaminating bands.…”

Section: Synthesis and Characterization Of Butadiene Diepoxidementioning

confidence: 99%

“…Cross-linked adducts are thought to be responsible for the observation that the diepoxide is considerably more mutagenic in mice than the monoepoxide under identical exposure conditions (1) and for the fact that butadiene is more genotoxic to mice than rats. The latter observation is attributed to the greater effectiveness of mice at metabolizing butadiene to the diepoxide (2). Both species appear to be equally susceptible to cytogenetic damage inflicted by butadiene diepoxide when the epoxide is introduced directly into isolated rat or mouse lymphocytes (splenic or peripheral blood) (3).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Butadiene-induced Intrastrand DNA Cross-links: A Possible Role in Deletion Mutagenesis

Carmical¹,

Kowalczyk²,

Zou³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

To initiate studies designed to identify the mutagenic spectrum associated with butadiene diepoxide-induced N 2 -N 2 guanine intrastrand cross-links, site specifically adducted oligodeoxynucleotides were synthesized in which the adducted bases were centrally located within the context of the human ras 12 codon. The two stereospecifically modified DNAs and the corresponding unmodified DNA were ligated into a single-stranded M13mp7L2 vector and transfected into Escherichia coli. Both stereoisomeric forms (R,R and S,S) of the DNA cross-links resulted in very severely decreased plaqueforming ability, along with an increased mutagenic frequency for both single base substitutions and deletions compared with unadducted DNAs, with the S,S stereoisomer being the most mutagenic. Consistent with decreased plaque formation, in vitro replication of DNA templates containing the cross-links by the three major E. coli polymerases revealed replication blockage by both stereoisomeric forms of the cross-links. The same DNAs that were used for replication studies were also assembled into duplex DNAs and tested as substrates for the initiation of nucleotide excision repair by the E. coli UvrABC complex. UvrABC incised linear substrates containing these intrastrand cross-links with low efficiency, suggesting that these lesions may be inefficiently repaired by the nucleotide excision repair system.Metabolic bioactivation of 1,3-butadiene results in a diepoxide. As a bifunctional electrophile, butadiene diepoxide is theoretically capable of producing inter-and intrastrand DNA-DNA cross-links. Cross-linked adducts are thought to be responsible for the observation that the diepoxide is considerably more mutagenic in mice than the monoepoxide under identical exposure conditions (1) and for the fact that butadiene is more genotoxic to mice than rats. The latter observation is attributed to the greater effectiveness of mice at metabolizing butadiene to the diepoxide (2). Both species appear to be equally susceptible to cytogenetic damage inflicted by butadiene diepoxide when the epoxide is introduced directly into isolated rat or mouse lymphocytes (splenic or peripheral blood) (3).There are a number of studies supporting the existence of butadiene diepoxide-induced interstrand cross-links (4 -9). Evidence for such cross-links is based largely on denaturation/ renaturation experiments in which interstrand-cross-linked DNA renatures more rapidly than noncross-linked. The only cross-linked species thus far identified, a guanine N7-guanine N7 cross-link, was isolated from salmon sperm DNA by Lawley and Brookes (8). In 1993, Millard and White (10) reported that synthetic oligonucleotide duplexes of varying sequences reacted rather diffusely with butadiene diepoxide but showed preference for interstrand cross-linking at 5Ј-GNC sites. As expected for guanine N7 cross-links most of the bands that migrated in denaturing gels in the region expected for dimeric structures were cleavable by piperidine at 90°C. However, some cross-linked material persis...

show abstract

“…In chronic inhalation experiments with B6C3F1 mice and Sprague-Dawley rats, BD was carcinogenic in both species (10,28). However, B6C3F1 mice developed tumors at BD exposure concentrations three orders of magnitude lower than those that cause cancer in Sprague-Dawley rats (10,(28)(29)(30). Furthermore, the mutational spectrum found in BD-induced tumors of mice was different from that in rats (31).…”

Section: Introductionmentioning

confidence: 99%

Quantitative High-Performance Liquid Chromatography−Electrospray Ionization−Tandem Mass Spectrometry Analysis of the Adenine−Guanine Cross-Links of 1,2,3,4-Diepoxybutane in Tissues of Butadiene-Exposed B6C3F1 Mice

Goggin

Anderson

Park

et al. 2008

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Abstract1,3-Butadiene (BD) is an important industrial chemical used in the rubber and plastics manufacture, as well as an environmental pollutant present in automobile exhaust and cigarette smoke. It is classified as a known human carcinogen based on the epidemiological evidence in occupationally exposed workers and its ability to induce tumors in laboratory animals. BD is metabolically activated to several reactive species, including 1,2,3,4-diepoxybutane (DEB) which is hypothesized to be the ultimate carcinogenic species due to its bifunctional electrophilic nature and its ability to form DNA-DNA and DNA-protein cross-links. While 1,4-bis-(guan-7-yl)-2,3,-butanediol (bis-N7G-BD) is the only type of DEB-specific DNA adduct previously quantified in vivo, four regioisomeric guanineadenine (G-A) cross-links have been observed in vitro, e.g. 1-(guan-7-yl)-4-(aden-1-yl)-2,3-butanediol (N7G-N1A-BD), 1-(guan-7-yl)-4-(aden-3-yl)-2,3,-butanediol (N7G-N3A-BD), 1-(guan-7-yl)-4-(aden-7-yl)-2,3-butanediol (N7G-N7A-BD), and 1-(guan-7-yl)-4-(aden-6-yl)-2,3-butanediol (N7G-N 6 A-BD) (Park et al., Chem. Res. Toxicol. 2004, 17, 1638-1651. The goal of the present work was to develop an isotope dilution HPLC-ESI + -MS/MS method for the quantitative analysis of guanine-adenine DEB cross-links in DNA extracted from BD-exposed laboratory animals. In our approach, G-A butanediol conjugates are released from the DNA backbone by thermal or mild acid hydrolysis. Following solid phase extraction, samples are subjected to capillary HPLCpositive mode electrospray ionization-tandem mass spectrometry (HPLC-ESI + -MS/MS) analysis with 15 N 3 , 13 C 1 -labeled internal standards. The detection limit of our current method is 0.6 to 1.5 adducts per 10 8 normal nucleotides. The new method was validated by spiking G-A cross-link standards (10 fmol each) into control mouse DNA (0.1 mg), followed by sample processing and HPLC-ESI + -MS/MS analysis. The accuracy and precision were calculated as 105 ± 17 %

show abstract

Metabolism of 1,3-butadiene: species differences

Cited by 61 publications

References 15 publications

Analysis of Diepoxide-Specific Cyclic N -Terminal Globin Adducts in Mice and Rats after Inhalation Exposure to 1,3-Butadiene

Analysis of Diepoxide-Specific Cyclic N -Terminal Globin Adducts in Mice and Rats after Inhalation Exposure to 1,3-Butadiene

Butadiene-induced Intrastrand DNA Cross-links: A Possible Role in Deletion Mutagenesis

Quantitative High-Performance Liquid Chromatography−Electrospray Ionization−Tandem Mass Spectrometry Analysis of the Adenine−Guanine Cross-Links of 1,2,3,4-Diepoxybutane in Tissues of Butadiene-Exposed B6C3F1 Mice

Contact Info

Product

Resources

About