Interactions of vinyl chloride with rat-liver DNA in vivo

Green, T.; Hathway, D. E.

doi:10.1016/0009-2797(78)90126-6

Cited by 108 publications

(36 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quantification of the standard is performed by UV spectroscopy using an extinction coefficient of 10,300 M -1 cm -1 at 260 nm. 42,43 dX and dO standards are synthesized by a modification of the method of Suzuki et al 45 Briefly, incubate 10 mM 2′-deoxyguanosine or [ 15 N 5 ]-2′-deoxyguanosine with 100 mM NaNO 2 in 0.3 M sodium acetate buffer (pH 3.7) at 37 °C for 6 h. dX and dO are purified by HPLC using a LUNA C18 reversed-phase column (250 × 3 mm, 5 μm particle size, 100 Å pore size; Phenomenex, Torrance, CA) with elution performed at a flow rate of 0.4 ml/min with 1% acetonitrile in 50 mM ammonium acetate (pH 7.4) for the first 5 min, followed by a linear gradient of 1-25% acetonitrile for 5 min; holding at 25% for 10 min; then a reversal of the gradient to 1% for 5 min; and finally eluting at 1% acetonitrile over the last 5 min. Fractions containing the products are dried under vacuum and redissolved in water followed by desalting on a second HPLC system consisting of a Haisil HL C18 reversed phase column (250 × 4.6 mm, 5 μm particle size, 100 Å pore size; Higgins Analytic Inc, Mountain View, CA) eluted with 5% acetonitrile in water at a flow rate of 0.4 ml/min, with elution confirmed using commercially available standards.…”

Section: Synthesis Of Internal Standardsmentioning

confidence: 99%

Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry

et al. 2008

View full text Add to dashboard Cite

The analysis of damage products as biomarkers of inflammation has been hampered by a poor understanding of the chemical biology of inflammation, the lack of sensitive analytical methods, and a focus on single chemicals as surrogates for inflammation. To overcome these problems, we developed a general and sensitive liquid chromatographic tandem mass spectrometry (LC/MS-MS) method to quantify, in a single DNA sample, the nucleoside forms of seven DNA lesions reflecting the range of chemistries associated with inflammation: 2′-deoxyuridine, 2′-deoxyxanthosine, and 2′-deoxyinosine from nitrosative deamination; 8-oxo-2′-deoxyguanosine from oxidation; and 1,N 2 -etheno-2′-deoxyguanosine, 1,N 6 -etheno-2′-deoxyadenosine, and 3,N 4 -etheno-2′-deoxycytidine arising from reaction of DNA with lipid peroxidation products. Using DNA purified from cells or tissues under conditions that minimize artifacts, individual nucleosides are purified by HPLC and quantified by isotope-dilution, electrospray ionization LC/MS-MS. The method can be applied to other DNA damage products and requires 4-6 days to complete depending upon the number of samples. Search terms

show abstract

Section: Synthesis Of Internal Standardsmentioning

confidence: 99%

Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry

et al. 2008

View full text Add to dashboard Cite

show abstract

“…2), which is a prerequisite of tumor initiation (24). Such interaction would be analogous to that of vinyl chloride with rat-liver DNA in vh'o, which forms imidazo derivatives with some nucleoside residues (16). Further work is in progress to investigate this hypothesis.…”

mentioning

confidence: 94%

Comparative mammalian metabolism of vinyl chloride and vinylidene chloride in relation to oncogenic potential.

Hathway¹

1977

Environ Health Perspect

View full text Add to dashboard Cite

Elucidation of the role of vinyl chloride metabolites in the various reaction sequences which comprise the metabolic pathway, including the interaction of reactive metabolites with some purine and pyrimidine residues of target-organ DNA, provides some explanation for the (oncogenic) properties associated with the original substance. Comparative investigation of the biological fate of vinylidene chloride reveals an agent of low oncogenic potential which is likely to be damaging only under special circumstances, and species differences which suggest that the mouse is more susceptible than the rat towards vinylidene chloride oncogenicity.The research work with which this communication is concerned is based on the idea that knowledge of the biology of the reactive metabolites of chemical carcinogens in the mammal, including the precise nature of the chemical changes to the DNA of the nucleus, ought to give an insight into the (oncogenic) properties of the parent compounds.In tracer studies, N-acetyl-S-(2-hydroxymethyl)-cysteine was shown to be a major vinyl chloride metabolite in rats, but according to the method of protective esterification that was used so a derivative either of N-acetyl-S-(2-chloroethyl)cysteine or of N-acetyl-S-(2-hydroxyethyl)cysteine was isolated from body fluids (1, 2). Thus, by Fischer-Speier methylation,N-acetyl-S-(2-chloroethyl)cysteine was obtained, and with diazomethane, N-acetyl-S-(2-hydroxyethyl)cysteine. It might be stated in passing that throughout the investigations described, mass spectrometry, involving electron impact (El) and chemical ionization sources and multiple-ion detection and all combinations of these facilities, was used extensively both for product identification and analysis and for the purposes of detection. Treatment of the 0-methyl ester of

show abstract

“…These include industrial chemicals such as vinyl chloride (1) and the widespread environmental compound ethyl carbamate (2,3). Ethyl carbamate is a carcinogen that is metabolized to vinyl carbamate, then oxidized by cytochrome P450 to the electrophyle vinyl carbamate epoxide that reacts with RNA and DNA bases to form etheno-bridged adducts (4)(5)(6).…”

mentioning

confidence: 99%

3, N ⁴ -ethenocytosine, a highly mutagenic adduct, is a primary substrate for Escherichia coli double-stranded uracil-DNA glycosylase and human mismatch-specific thymine-DNA glycosylase

Saparbaev

Laval²

1998

Proc. Natl. Acad. Sci. U.S.A.

165

170

View full text Add to dashboard Cite

Exocyclic DNA adducts are generated in cellular DNA by various industrial pollutants such as the carcinogen vinyl chloride and by endogenous products of lipid peroxidation. The etheno derivatives of purine and pyrimidine bases 3,N 4 -ethenocytosine (C), 1,N 6 -ethenoadenine (A), N 2 ,3-ethenoguanine, and 1,N 2 -ethenoguanine cause mutations. The A residues are excised by the human and the Escherichia coli 3-methyladenine-DNA glycosylases (ANPG and AlkA proteins, respectively), but the enzymes repairing C residues have not yet been described. We have identified two homologous proteins present in human cells and E. coli that remove C residues by a DNA glycosylase activity. The human enzyme is an activity of the mismatch-specific thymine-DNA glycosylase (hTDG). The bacterial enzyme is the double-stranded uracil-DNA glycosylase (dsUDG) that is the homologue of the hTDG. In addition to uracil and C-DNA glycosylase activity, the dsUDG protein repairs thymine in a G͞T mismatch. The fact that C is recognized and efficiently excised by the E. coli dsUDG and hTDG proteins in vitro suggests that these enzymes may be responsible for the repair of this mutagenic lesion in vivo and be important contributors to genetic stability.

show abstract

Interactions of vinyl chloride with rat-liver DNA in vivo

Cited by 108 publications

References 24 publications

Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry

Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry

Comparative mammalian metabolism of vinyl chloride and vinylidene chloride in relation to oncogenic potential.

3, N ⁴ -ethenocytosine, a highly mutagenic adduct, is a primary substrate for Escherichia coli double-stranded uracil-DNA glycosylase and human mismatch-specific thymine-DNA glycosylase

Contact Info

Product

Resources

About

Interactions of vinyl chloride with rat-liver DNA in vivo

Cited by 108 publications

References 24 publications

Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry

Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry

Comparative mammalian metabolism of vinyl chloride and vinylidene chloride in relation to oncogenic potential.

3, N 4 -ethenocytosine, a highly mutagenic adduct, is a primary substrate for Escherichia coli double-stranded uracil-DNA glycosylase and human mismatch-specific thymine-DNA glycosylase

Contact Info

Product

Resources

About

3, N ⁴ -ethenocytosine, a highly mutagenic adduct, is a primary substrate for Escherichia coli double-stranded uracil-DNA glycosylase and human mismatch-specific thymine-DNA glycosylase