Hepatic microsomal metabolism of 1,3-butadiene

Malvoisin, Etienne; Roberfroid, Marcel

doi:10.3109/00498258209046787

Cited by 147 publications

(83 citation statements)

References 13 publications

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“…These may be further oxidized by cytochrome P450 2E1 or 3A4 to form 1,2:3,4-diepoxybutanes (BDO 2 ) (25,(27)(28)(29)(30)(31). 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).…”

Section: Introductionmentioning

confidence: 99%

“…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%

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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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Section: Introductionmentioning

confidence: 99%

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.

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“…Both compounds induce increases in the frequency of sister chromatid exchanges in bone marrow cells and in the levels of micronucleated erythrocytes in peripheral blood of mice (7,18); both compounds can be metabolized to monoepoxide and diepoxide intermediates by liver microsomal monooxygenases (8,9,19,20), the diepoxide intermediates of both compounds are mutagenic in Salmonella (10,21); both compounds cause reductions in red blood cell counts, hemoglobin concentrations, and volume of packed red cells in mice; and both compounds produced olfactory epithelial changes, testicular atrophy, and forestomach epithelial hyperplasia in mice. Due to these similarities, 13- exposure studies of isoprene at concentrations ranging from 70 to 7000 ppm have been initiated in F344 rats and B6C3F1 mice to determine whether isoprene acts similar to 1,3-butadiene after longer exposure durations.…”

Section: Discussionmentioning

confidence: 99%

Inhalation Toxicology of Isoprene in F344 Rats and B6C3F 1 Mice Following Two-Week Exposures

Melnick¹,

Roycroft²,

Chou³

et al. 1990

Environmental Health Perspectives

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Isoprene (2-methyl-1,3-butadiene) was selected for toxicologic evaluations because of its structural similarity to 1,3-butadiene, a potent rodent carcinogen. Two-week inhalation toxicology studies of isoprene were conducted in F344 rats and B6C3F1 mice at exposure concentrations of 0, 438, 875, 1750, 3500, or 7000 ppm. For rats, there were no chemically related changes in survival, body weight gain, clinical signs, hematologic or clinical chemistry parameters, or gross or microscopic lesions. Exposure of mice to isoprene did not produce mortalities and only caused a decrease in body weight gain for male mice in the 7000 ppm exposure group; however, hematologic changes and microscopic lesions including testicular atrophy, olfactory epithelial degeneration, and forestomach epithelial hyperplasia were observed in isoprene-exposed mice. Similar toxicologic effects have been previously observed in B6C3F1 mice exposed to 1,3-butadiene. A species difference in susceptibility between rats and mice exposed to isoprene was evident in these short-term exposure studies.

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“…It is found to be carcinogenic in B63F1 mice with the lowest concentration tested (6.25 ppm) (59). The conversion of 1,3-butadiene to the reactive metabolites 1,2-epoxy-3-butane and dieposidebutane have been identified in rats and mice (60).…”

Section: Initiatd or Predisposed Cell; Diminishing Opportunity For Gementioning

confidence: 99%

Application of integrated genetic monitoring: the optimal approach for detecting environmental carcinogens.

Legator

1994

Environ Health Perspect

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Short-term in vitro genetic toxicity assays have not fulfilled their anticipated role in predicting the carcinogenicity of environmental agents reliably and economically. A reduction in emphasis from nonanimal systems to relevant animal assays and population monitoring will help to reestablish the credibility of this field. An analysis of the various steps in the carcinogenic process indicates the biological responses occurring during these stages can be utilized for early detection of environmental carcinogens. Emphasis should be placed on using the earliest significant response that indicates genetic damage (e.g., gene mutations and chromosome alterations). Assays that detect pregenomic damage (e.g., adduct formation), without evidence of subsequent heritable genetic alterations, may produce misleading results for risk assessment and should not be considered as stand-alone monitoring procedures. Late biological responses may occur in tissues or organs where genetic damage may be difficult to measure, and the opportunity for intervention diminishes as we approach the clinical outcome. For example, analyzing localized cells that contain activated protooncogenes and inactivated tumor suppressor genes, although they further document adverse response from exposure to carcinogens, may be of greater value for indicating clinical outcome than for genetic monitoring. With few notable exceptions, the window of opportunity for genetic monitoring is the period after exposure where genetic damage is evident and where circulating lymphocytes can faithfully record this damage. An ongoing study of butadiene-exposed workers illustrates an optimum protocol, where multiple assays can be carried out and correlated with both external and internal measurements of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hepatic microsomal metabolism of 1,3-butadiene

Cited by 147 publications

References 13 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

Inhalation Toxicology of Isoprene in F344 Rats and B6C3F 1 Mice Following Two-Week Exposures

Application of integrated genetic monitoring: the optimal approach for detecting environmental carcinogens.

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Hepatic microsomal metabolism of 1,3-butadiene

Cited by 147 publications

References 13 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

Inhalation Toxicology of Isoprene in F344 Rats and B6C3F 1 Mice Following Two-Week Exposures

Application of integrated genetic monitoring: the optimal approach for detecting environmental carcinogens.

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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

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