Isolation of urinary 3-methyladenine using immunoaffinity columns prior to determination by low-resolution gas chromatography-mass spectrometry

Friesen, Marlin D.; Garren, Liliane; Prévost, Virginie; Shuker, David E. G.

doi:10.1021/tx00019a014

Cited by 41 publications

(16 citation statements)

References 5 publications

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“…Prior studies have demonstrated that alkylated, polycyclic hydrocarbon, and aflatoxin adducts are stable in vivo, whereas the chemotherapeutic agent O 6 -benzylguanine is oxidized (21,(26)(27)(28). The site of oxidation on O 6 -benzylguanine is the 8 position of the imidazole ring, which is different from the site of oxidation on M 1 dG.…”

Section: Discussionmentioning

confidence: 99%

In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M ₁ dG

Otteneder¹,

Knutson²,

Daniels³

et al. 2006

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

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3-(2-Deoxy-␤-D-erythro-pentofuranosyl)pyrimido[1,2-␣]purin-10(3H)-one (M1dG) is a DNA adduct arising from the reaction of 2-deoxyguanosine with the lipid peroxidation product, malondialdehyde, or the DNA peroxidation product, base propenal. M 1dG is mutagenic in bacteria and mammalian cells and is present in the genomic DNA of healthy human beings. It is also detectable, albeit at low levels, in the urine of healthy individuals, which may make it a useful biomarker of DNA damage linked to oxidative stress. We investigated the possibility that the low urinary levels of M 1dG reflect metabolic conversion to derivatives. M 1dG was rapidly removed from plasma (t1/2 ‫؍‬ 10 min) after i.v. administration to rats. A single urinary metabolite was detected that was identified as 6-oxo-M 1dG by MS, NMR spectroscopy, and independent chemical synthesis. 6-Oxo-M1dG was generated in vitro by incubation of M 1dG with rat liver cytosols, and studies with inhibitors suggested that xanthine oxidase and aldehyde oxidase are involved in the oxidative metabolism. M1dG also was metabolized by three separate human liver cytosol preparations, indicating 6-oxo-M1dG is a likely metabolite in humans. This represents a report of the oxidative metabolism of an endogenous DNA adduct and raises the possibility that other endogenous DNA adducts are metabolized by oxidative pathways. 6-Oxo-M1dG may be a useful biomarker of endogenous DNA damage associated with inflammation, oxidative stress, and certain types of cancer chemotherapy.excretion ͉ inflammation ͉ DNA damage ͉ oxidation ͉ metabolite D NA damage from endogenous sources is believed to contribute significantly to human genetic diseases, including cancer (1, 2). A major cause of endogenous DNA damage is oxidation (3, 4). Agents such as hydroxyl radical or peroxynitrous acid oxidize nucleic acid bases or the deoxyribose backbone to form miscoding lesions or induce strand breaks (5). In addition, oxidation of other cellular constituents (i.e., lipid, protein) generates reactive derivatives that form adducts with nucleic acid bases (1). In the absence of repair, this panoply of damage results in mutations, triggers signaling to arrest cell division, or induces apoptosis.3-(2-Deoxy-␤-D-er ythro-pentofuranosyl)pyrimido[1,2-␣]purin-10(3H)-one (M 1 dG) is an adduct found at varying levels in genomic DNA of rodents and humans (6-8). It is derived from the lipid oxidation product, malondialdehyde, or the DNA oxidation product, base propenal (Scheme 1) (9-11). M 1 dG is miscoding when assayed by in vitro DNA replication and is mutagenic in bacterial and mammalian cells (12)(13)(14). It induces base pair substitutions (M 1 dG3T and M 1 dG3A) and frameshift mutations in reiterated sequences (e.g., CG n ) when shuttle vectors containing a site-specific lesion are replicated in COS-7 cells (14). Genetic and biochemical experiments indicate that M 1 dG is removed by nucleotide excision repair in both bacterial and mammalian cells (13-15).As a prerequisite for preclinical, clinical, and populationbased ...

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Section: Discussionmentioning

confidence: 99%

In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M ₁ dG

Otteneder¹,

Knutson²,

Daniels³

et al. 2006

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

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“…Immunosorbent preparation followed the previously published method [25], with some modification. Briefly, 1.5 g of protein Asepharose CL 4B was dissolved in 100 mL of water and poured into a sintered-glass funnel (40-60 m).…”

Section: Immunosorbent Preparationmentioning

confidence: 99%

“…The IAC gel was prepared by means of directional coupling method [25]. The IgG fraction from the antiserum was conjugated to protein A-sepharose CL 4B by using a bifunctional cross-linking agent, dimethyl pimelimidate.…”

Section: Preparation Of Iac Columnmentioning

confidence: 99%

Simultaneous determination of thiamphenicol, florfenicol and florfenicol amine in swine muscle by liquid chromatography–tandem mass spectrometry with immunoaffinity chromatography clean-up

Luo

Xia

Liang

et al. 2010

Journal of Chromatography B

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“…A similar dose-response relationship to that described above for urinary d3-7-MeGua was seen for the excretion of d3-3-MeAde in rats after coadministration of combinations of d6-AP and nitrite (13). These results, in combination with recent improvements in analytical methodology using immunoaffinity purification of 3-MeAde (14), suggest that d6-AP could be a useful probe drug for studies on endogenous nitrosation in experimental animals (AP cannot be used as a probe drug in humans due to its toxicity). Studies are currently underway in our laboratory to evaluate the role of parasitic infections in endogenous nitrosation using d6-AP in experimental models.…”

Section: Introductionmentioning

confidence: 91%

Noninvasive methods for measuring DNA alkylation in experimental animals and humans.

Shuker

Prévost

Friesen

et al. 1993

Environ Health Perspect

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Alkylpurines are liberated from alkylated DNA by glycosylase repair enzymes and, in most cases, excreted in urine without further metabolism. This phenomenon forms the basis of noninvasive methods to measure DNA alkylation in vivo. In the case of methyl adducts, such as 7-methylguanine (7-MeGua), natural backgrounds exist due to RNA turnover. However, deuterated (d3) methylating agents or precursors give rise to d3-7-MeGua and d3-3-methyladenine (3-MeAde), which can be readily quantitated using gas chromatography-mass spectrometry (GC-MS). A deuterated probe drug, such as d6-aminopyrine, can be used to measure endogenous nitrosation levels in experimental animals. In contrast, for higher alkyl homologues of alkylpurines, natural backgrounds are low or nonexistent and can be directly measured by GC-MS using stable isotope labeled internal standards. For example, increased levels of urinary 3-ethyladenine were observed in cigarette smokers. Due to recent advances in analytical methodology, notably immunoaffinity cleanup of urine, measurements of excreted DNA adducts can be used in studies in human populations exposed to low levels of alkylating carcinogens.

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Isolation of urinary 3-methyladenine using immunoaffinity columns prior to determination by low-resolution gas chromatography-mass spectrometry

Cited by 41 publications

References 5 publications

In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M ₁ dG

In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M ₁ dG

Simultaneous determination of thiamphenicol, florfenicol and florfenicol amine in swine muscle by liquid chromatography–tandem mass spectrometry with immunoaffinity chromatography clean-up

Noninvasive methods for measuring DNA alkylation in experimental animals and humans.

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Isolation of urinary 3-methyladenine using immunoaffinity columns prior to determination by low-resolution gas chromatography-mass spectrometry

Cited by 41 publications

References 5 publications

In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M 1 dG

In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M 1 dG

Simultaneous determination of thiamphenicol, florfenicol and florfenicol amine in swine muscle by liquid chromatography–tandem mass spectrometry with immunoaffinity chromatography clean-up

Noninvasive methods for measuring DNA alkylation in experimental animals and humans.

Contact Info

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In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M ₁ dG

In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M ₁ dG