32P-postlabeling of 1,3-butadiene and 4-vinyl-1-cyclohexene metabolite-DNA adducts: in vitro and in vivo applications

Mabon, N.; Randerath, Kurt

doi:10.1016/0300-483x(96)03470-1

Cited by 9 publications

(2 citation statements)

References 6 publications

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“…The N-7 guanine adducts of EB (24)(25)(26)(27)(28)(29)(30)(31) and DEB (32), N-1, N-3, N 6 , and N-7 adenine adducts of EB (30,31,(33)(34)(35), and N-3, N 6 , N-7, and N-9 adenine adducts of DEB (36)(37)(38) and N-3-thymidine adducts of EB (39) have been characterized. LC/ESI + /MS/MS (40,41) and 32 P-postlabeling (27,28,34,35,37,(42)(43)(44)(45) combined with chromatographic separation have been used to characterize and/or quantitate the adducts formed in vitro by EB and DEB. There have also been several reports of BD-induced adduct formation in vivo.…”

Section: Introductionmentioning

confidence: 99%

Molecular Dosimetry of N-7 Guanine Adduct Formation in Mice and Rats Exposed to 1,3-Butadiene

Koç

Tretyakova

Walker

et al. 1999

Chem. Res. Toxicol.

126

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1,3-Butadiene (BD) is a high-volume chemical used in the production of rubber and plastic. BD is a potent carcinogen in mice and a much weaker carcinogen in rats, and has been classified as a probable human carcinogen. Upon metabolic activation in vivo, it forms DNA-reactive metabolites, 1,2-epoxy-3-butene (EB), 1,2:3, 4-diepoxybutane (DEB), and 3,4-epoxy-1,2-butanediol (EBD). The molecular dosimetry of N-7 guanine adduct formation by these metabolites of BD in liver, lung, and kidney of B6C3F1 mice and F344 rats exposed to 0, 20, 62.5, or 625 ppm BD was studied. The adducts, racemic and meso forms of N-7-(2,3,4-trihydroxybut-1-yl)guanine (THB-Gua), N-7-(2-hydroxy-3-buten-1-yl)guanine (EB-Gua I), and N-7-(1-hydroxy-3-buten-2-yl)guanine (EB-Gua II), were isolated from DNA by neutral thermal hydrolysis, desalted on solid-phase extraction cartridges, and quantitated by LC/ESI(+)/MS/MS. The number of adducts per 10(6) normal guanine bases for a given adduct was higher in mice than rats exposed to 625 ppm BD, but generally similar at lower levels of exposure. The THB-Gua adducts were the most abundant (6-27 times higher than EB-Gua) and exhibited a nonlinear exposure-response relationship. In rats, the exposure-response curves for the formation of THB-Gua adducts reached a plateau after 62.5 ppm, suggesting saturation of metabolic activation. The number of THB-Gua adducts continued to increase in mice between 62.5 and 625 ppm BD. In contrast, the less common EB-Gua adducts had a linear exposure-response relationship in both species. Combining the information from this study with previous data on BD metabolism, we were able to estimate the number of THB-Gua that resulted from DEB and EBD, and conclude that most of the THB-Gua is formed from EBD. We hypothesize that most of the EBD arises from the immediate conversion of DEB to EBD within the endoplasmic reticulum. This study highlights the need for measurements of the levels of EBD in tissues of rats and mice and for the development of a unique biomarker for DEB that is available for binding to DNA.

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Section: Introductionmentioning

confidence: 99%

Molecular Dosimetry of N-7 Guanine Adduct Formation in Mice and Rats Exposed to 1,3-Butadiene

Koç

Tretyakova

Walker

et al. 1999

Chem. Res. Toxicol.

126

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“…A number of adenine and guanine DNA adducts of 1,2-epoxybutene, 1,2:3,4-diepoxybutane, and 3,4-epoxy-1,2-butanediol, the reactive metabolites of butadiene, have been identified by different assays. A widely used method, the 32 P-postlabeling assay, includes the enzymatic digestion of DNA to nucleotides, 5' labeling of these nucleotides with an isotopically labeled phosphate group, and the resolution and detection of the labeled products, generally by thin-layer chromatography or high-performance liquid chromatography (HPLC) (440)(441)(442)(443)(444)(445)(446). Other methods used to detect and measure DNA adducts of butadiene include liquid chromatography in combination with tandem mass spectrometry (447), and HPLC separation and analysis of adducts by UV spectrophotometry, electrospray ionization mass spectrometry, nuclear magnetic resonance (NMR), and/or fastatom-bombardment mass spectrometry (448)(449)(450).…”

Section: Biomonitoring/biomarkersmentioning

confidence: 99%

Aliphatic Hydrocarbons

Carreón¹,

Herrick²

2012

Patty's Toxicology

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Aliphatic hydrocarbons are open‐chain compounds that may be saturated or unsaturated. The saturated compounds, known as paraffin hydrocarbons or alkanes , include methane and its homologs having the empirical formula C n H 2 n +2 . The unsaturated compounds fall into a number of homologous series: ( 1 ) those containing one double bond (ethylene and its homologs) and having the formula C n H 2 n are known as olefins or alkenes ; ( 2 ) those containing one triple bond (acetylene and its homologs) are called acetylenes or alkynes and have the formula C n H 2 n −2 ; ( 3 ) those having two double bonds (allene, 1,3‐butadiene and 1,4‐pentadiene represent three types) are diolefins or alkadienes and also have the formula C n H 2 n −2 ; ( 4 ) those having a large number of double or triple bonds or both double and triple bonds are named in analogous fashion as alkatrienes , alkatetraenes , alkadiynes , alkenynes , and alkadienynes . Aliphatic hydrocarbons are asphyxiants and central nervous system ( CNS ) depressants. Serious toxic effects of aliphatic hydrocarbons include asphyxia and chemical pneumonitis for many paraffins, axonal neuropathy for n ‐hexane, and cancer for 1,3‐butadiene.

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Aliphatic Hydrocarbons

Carreón¹

2001

Patty's Toxicology

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Aliphatic hydrocarbons are open‐chain compounds that may be saturated or unsaturated. The saturated compounds, known as paraffin hydrocarbons or alkanes , include methane and its homologs having the empirical formula C n H 2 n +2 . The unsaturated compounds fall into a number of homologous series: ( 1 ) those containing one double bond (ethylene and its homologs) and having the formula C n H 2 n are known as olefins or alkenes ; ( 2 ) those containing one triple bond (acetylene and its homologs) are called acetylenes or alkynes and have the formula C n H 2 n −2 ; ( 3 ) those having two double bonds (allene, 1,3‐butadiene, and 1,4‐pentadiene represent three types) are diolefins or alkadienes and also have the formula C n H 2 n −2 ; ( 4 ) those having a large number of double or triple bonds or both double and triple bonds are named in analogous fashion as alkatrienes , alkatetraenes , alkadiynes , alkenynes , and alkadienynes . Aliphatic hydrocarbons are asphyxiants and central nervous system (CNS) depressants. Serious toxic effects of aliphatic hydrocarbons include asphyxia and chemical pneumonitis for many paraffins, axonal neuropathy for n ‐hexane, and cancer for 1,3‐butadiene.

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32P-postlabeling of 1,3-butadiene and 4-vinyl-1-cyclohexene metabolite-DNA adducts: in vitro and in vivo applications

Cited by 9 publications

References 6 publications

Molecular Dosimetry of N-7 Guanine Adduct Formation in Mice and Rats Exposed to 1,3-Butadiene

Molecular Dosimetry of N-7 Guanine Adduct Formation in Mice and Rats Exposed to 1,3-Butadiene

Aliphatic Hydrocarbons

Aliphatic Hydrocarbons

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