Toxicology and Epidemiology of 1,3-Butadiene

Himmelstein, Matthew W.; Acquavella, John F.; Recio, Leslie; Medinsky, Michele A.; Bond, James A.

doi:10.3109/10408449709037482

Cited by 188 publications

(154 citation statements)

References 148 publications

Supporting

Mentioning

153

Contrasting

Order By: Relevance

“…The International Agency for Cancer Research (IARC) lists BD as a "probable human carcinogen" (Group 2A) (10-12). Chronic human exposure in the SBR industry may induce genotoxic effects (13)(14)(15) and is correlated with increased risk for leukemia (1,(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

show abstract

“…1,3-Butadiene is an important industrial chemical used in the production of synthetic rubber and is also found in gasoline, cigarette smoke, and auto exhaust and as a product of combustion of wood and fossil fuels (1). It is a potent carcinogen in mice and a weak carcinogen in rats (1).…”

Section: Introductionmentioning

confidence: 99%

“…It is a potent carcinogen in mice and a weak carcinogen in rats (1). Epidemiologic studies have shown an increased incidence of leukemia and lymphohematopoietic cancers in 1,3-butadiene-exposed workers (1).…”

Section: Introductionmentioning

confidence: 99%

“…Epidemiologic studies have shown an increased incidence of leukemia and lymphohematopoietic cancers in 1,3-butadiene-exposed workers (1). 1,3-Butadiene requires metabolic activation for its carcinogenicity (1). The major metabolites of 1,3-butadiene are 1,2-epoxy-3-butene, 3-butene-1,2-diol, 1,2;3,4-diepoxybutane, and 3,4-epoxy-1,2-butanediol (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

“…[2][3][4] Its toxicity on human beings was also studied. 5) Most of the toxicity studies were conducted on butadiene and isoprene 6) but not on the chemicals cis-pieperlylene, trans-piperylene (isomers of 1,3-pentadiene), 2,4-hexadiene or 1,4-pentadiene-3-ol. These chemicals are structurally related to 1,3-butadiene which contains carbon double bond.…”

Section: Introductionmentioning

confidence: 99%

MutagenicityTesting of 1,3-Butadiene, 1,4-Pentadiene-3-ol, Isoprene, 2,4-Hexadiene, cis- and trans-Piperlylene.

Madhusree¹,

Goto

Ohkubo³

et al. 2002

JOURNAL OF HEALTH SCIENCE

View full text Add to dashboard Cite

A mutagenicity test was conducted for 1,4-pentadiene-3-ol, 2,4-hexadiene, isoprene, cis-and transpiperylene in the bacterial mutation assay using Salmonella typhimurium (S. typhimurium) strain TA 100, TA98, TA1535 and Escherichia coli (E. coli) WP2uvrA/ pKM101 with and without metabolic activation by S9 mix in the preincubation method. The mutagenicity of 1,3-butadiene was tested by the gas exposure method. Mutagenicity was weakly positive for 1,4-pentadiene-3-ol in TA 100 with S9 mix and was pseudopositive for WP2uvrA/pKM101 without S9 mix. Mutagenicity was very clear for 1,3-butadiene in 10 fold concentrated TA1535 with S9 mix. The 2,4-hexadiene, isoprene, cispiperlylene and trans-piperlylene were not mutagenic on S. typhimurium TA98, TA100, TA1535 or E. coli WP2uvrA/pKM101 with or without metabolic activation. It can be concluded from these results, that chemicals, containing double bond carbon (C=C) chemical generally tend to show weak mutagenicity in the presence of the metabolic activation system.

show abstract

Toxicology and Epidemiology of 1,3-Butadiene

Cited by 188 publications

References 148 publications

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

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

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

MutagenicityTesting of 1,3-Butadiene, 1,4-Pentadiene-3-ol, Isoprene, 2,4-Hexadiene, cis- and trans-Piperlylene.

Contact Info

Product

Resources

About

Toxicology and Epidemiology of 1,3-Butadiene

Cited by 188 publications

References 148 publications

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

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

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

MutagenicityTesting of 1,3-Butadiene, 1,4-Pentadiene-3-ol, Isoprene, 2,4-Hexadiene, cis- and trans-Piperlylene.

Contact Info

Product

Resources

About

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

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