Mutagenic potential of adenine N6 adducts of monoepoxide and diolepoxide derivatives of butadiene

Carmical, J. Russ; Nechev, Lubomir V.; Harris, Constance M.; Harris, Thomas M.; Lloyd, R. Stephen

doi:10.1002/(sici)1098-2280(2000)35:1<48::aid-em7>3.0.co;2-c

Cited by 60 publications

(102 citation statements)

References 28 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 The N 6 dA-butanetriol adduct has been reported in vivo in humans exposed to BD 50 but the stereochemistry is unknown. Individual stereoisomers of the N 6 dA-butanetriol adduct have been examined and concluded to be only very weakly mutagenic, 51 consistent with our findings with these polymerases.…”

Section: Discussionsupporting

confidence: 86%

Replication past the Butadiene Diepoxide-Derived DNA Adduct S-[4-(N⁶-Deoxyadenosinyl)-2,3-dihydroxybutyl]glutathione by DNA Polymerases

Cho

Guengerich

2013

Chem. Res. Toxicol.

View full text Add to dashboard Cite

1,2,3,4-Diepoxybutane (DEB), a metabolite of the carcinogen butadiene, has been shown to cause glutathione (GSH)-dependent base-substitution mutations, especially A:T to G:C in Salmonella typhimurium TA1535 (Chem. Res. Toxicol. 23, 1544 (2010)) and Escherichia coli TRG8 cells (Chem. Res. Toxicol. 25, 1522 (2012)). We previously identified S-[4-(N6-deoxyadenosinyl)-2,3-dihydroxybutyl]GSH (N6dA-(OH)2butyl-GSH) as a major adduct in the reaction of S-(2-hydroxy-3,4-epoxybutyl)glutathione (DEB-GSH conjugate) with nucleosides and calf thymus DNA and in vivo in livers of mice and rats treated with DEB (Chem. Res. Toxicol. 25, 706 (2012)). For investigation of the miscoding potential of the major DEB-GSH conjugate-derived DNA adduct (N6dA-(OH)2butyl-GSH) and the effect of GSH conjugation on replication of DEB, extension studies were performed in duplex DNA substrates containing the site specifically-incorporated N6dA-(OH)2butyl-GSH adduct, N6-(2,3,4-trihydroxybutyl)deoxyadenosine adduct (N6dA-butanetriol), or unmodified deoxyadenosine (dA) by human DNA polymerases (Pol) η, ι, and κ, bacteriophage polymerase T7, and Sulfolobus solfataricus polymerase Dpo4. Although dTTP incorporation was the most preferred addition opposite the N6dA-(OH)2butyl-GSH adduct, N6dA-butanetriol adduct, or unmodified dA by all polymerases, dCTP misincorporation frequency opposite N6dA-(OH)2butyl-GSH was significantly higher than that opposite the N6dA-butanetriol adduct or unmodified dA by Pol κ or Pol T7. LC-MS/MS analysis of full-length primer extension products confirmed that Pol κ or Pol T7 incorporated the incorrect base C opposite N6dA-(OH)2butyl-GSH lesion. These results indicate the relevance of GSH-containing adducts for the A:T to G:C mutations produced by DEB.

show abstract

Section: Discussionsupporting

confidence: 86%

Replication past the Butadiene Diepoxide-Derived DNA Adduct S-[4-(N⁶-Deoxyadenosinyl)-2,3-dihydroxybutyl]glutathione by DNA Polymerases

Cho

Guengerich

2013

Chem. Res. Toxicol.

View full text Add to dashboard Cite

show abstract

“…Previously, we reported the mutagenic frequencies of butadiene-induced N 2 -guanine and N 6 -adenine adducts using the same system described herein (14,21). Whereas the monoadducted guanine lesions were much more blocking to replication and an order of magnitude more mutagenic, both adducts resulted in a Ͻ1% mutagenic frequency with no evidence for deletions.…”

Section: Discussionmentioning

confidence: 83%

“…3. On average, the mutation frequencies corresponding to the cross-links exceeded those of the monobase guanine adducts by an order of magnitude (14,21). However, it should be emphasized that the plaque-forming ability was down by more than four orders of magnitude relative to the unadducted DNAs.…”

Section: Synthesis and Characterization Of Butadiene Diepoxidementioning

confidence: 95%

“…The resulting plaques were then transferred to nitrocellulose filters in four successive lifts for each plate. These filters were then processed as described previously (14,21). The plaques were subsequently screened for possible base substitutions at position 2 of the ras 12 codon via differential hybridization techniques (18 -21).…”

Section: In Vivo Replication Of 13-butadiene-modified Circular Dnamentioning

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

Self Cite

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

“…The mutagenicity of the dG-EB adducts has been studied in an E. coli system (28,67). A, T, and G could all be incorporated opposite the adducts, with moderate stereoisomeric effects.…”

Section: Figmentioning

confidence: 99%

Kinetics of Nucleotide Incorporation Opposite DNA Bulky Guanine N2 Adducts by Processive Bacteriophage T7 DNA Polymerase (Exonuclease–) and HIV-1 Reverse Transcriptase

Hong

Harris

Guengerich

2005

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Six oligonucleotides with carcinogen derivatives bound at the N2 atom of deoxyguanosine were prepared, including adducts derived from butadiene, acrolein, crotonaldehyde, and styrene, and examined for effects on the replicative enzymes bacteriophage DNA polymerase T7 ؊ (T7 ؊ ) and HIV-1 reverse transcriptase for comparison with previous work on smaller DNA adducts. All of these adducts strongly blocked dCTP incorporation opposite the adducts. dATP was preferentially incorporated opposite the acrolein and crotonaldehyde adducts, and dTTP incorporation was preferred at the butadiene-and styrene-derived adducts. Steady-state kinetic analysis indicated that the reduced catalytic efficiency with adducted DNA involved both an increased K m and attenuated k cat . Fluorescence estimates of K d and pre-steady-state kinetic measurements of k off showed no significantly decreased affinity of T7 ؊ with the adducted oligonucleotides or the dNTP. Pre-steadystate kinetics showed no burst phase kinetics for dNTP incorporation with any of the modified oligonucleotides. These results indicate that phosphodiester bond formation or a conformational change of the enzyme⅐ DNA complex is rate-limiting instead of the step involving release of the oligonucleotide. Thio elemental effects for dNTP incorporation were generally relatively small but variable, indicating that the presence of adducts may sometimes make phosphodiester bond formation rate-limiting but not always.

show abstract

Mutagenic potential of adenine N6 adducts of monoepoxide and diolepoxide derivatives of butadiene

Cited by 60 publications

References 28 publications

Replication past the Butadiene Diepoxide-Derived DNA Adduct S-[4-(N⁶-Deoxyadenosinyl)-2,3-dihydroxybutyl]glutathione by DNA Polymerases

Replication past the Butadiene Diepoxide-Derived DNA Adduct S-[4-(N⁶-Deoxyadenosinyl)-2,3-dihydroxybutyl]glutathione by DNA Polymerases

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

Kinetics of Nucleotide Incorporation Opposite DNA Bulky Guanine N2 Adducts by Processive Bacteriophage T7 DNA Polymerase (Exonuclease–) and HIV-1 Reverse Transcriptase

Contact Info

Product

Resources

About

Mutagenic potential of adenine N6 adducts of monoepoxide and diolepoxide derivatives of butadiene

Cited by 60 publications

References 28 publications

Replication past the Butadiene Diepoxide-Derived DNA Adduct S-[4-(N6-Deoxyadenosinyl)-2,3-dihydroxybutyl]glutathione by DNA Polymerases

Replication past the Butadiene Diepoxide-Derived DNA Adduct S-[4-(N6-Deoxyadenosinyl)-2,3-dihydroxybutyl]glutathione by DNA Polymerases

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

Kinetics of Nucleotide Incorporation Opposite DNA Bulky Guanine N2 Adducts by Processive Bacteriophage T7 DNA Polymerase (Exonuclease–) and HIV-1 Reverse Transcriptase

Contact Info

Product

Resources

About

Replication past the Butadiene Diepoxide-Derived DNA Adduct S-[4-(N⁶-Deoxyadenosinyl)-2,3-dihydroxybutyl]glutathione by DNA Polymerases

Replication past the Butadiene Diepoxide-Derived DNA Adduct S-[4-(N⁶-Deoxyadenosinyl)-2,3-dihydroxybutyl]glutathione by DNA Polymerases