Measurement of DNA Adducts by Immunoassays

Poirier, Miriam C.; Weston, Ainsley; Gupta-Burt, Shalina; Reed, Eddie

doi:10.1007/978-1-4613-0637-5_1

Cited by 3 publications

(3 citation statements)

References 21 publications

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“…Reference standards of DNA adducts can serve as UV markers for chromatography-based molecular dosimetry (11), can be used as haptens for the development of immunoassays (15), can be used for development of 32Ppostlabeling standards (14), or can serve as reference compounds for mass spectral analysis (22). In some cases, DNA adducts can be obtained by direct reaction of an ultimate carcinogen with DNA or its monomers.…”

Section: Resultsmentioning

confidence: 99%

“…The lack of information on structures of DNA adducts derived from mononuclear arylamines, and the limited number of synthetic methods to generate significant quantities of such adducts, prompted this study on methods for generation of (purin-8-yl)arylamine adducts. With the availability of high specific activity tracer methods (22), with the 32P-postlabeling technique (14), or with antibody-based assays (15), it is possible to quantitatively characterize the formation of specific DNA adducts that exist at very low levels, but unambiguous identification of the materials detected has been hampered by a paucity of reference standards. Once purinearylamine base adducts have been prepared, they can be converted to deoxynucleosides and deoxynucleotides with appropriate blocking/deblocking strategies and existing chemical glycosylation and phosphorylation schemes (16- 18); enzymatic methods at this time appear to be ineffective for C-8-substituted purines (19).…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of N-(purin-8-yl)arylamines

Swenson

El‐Bayoumy

Shuie

et al. 1993

Chem. Res. Toxicol.

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Methods for direct synthesis of N-(purin-8-yl)arylamines were investigated. N-(Purin-8-yl)arylamines are adducts from reaction of electrophilic metabolites of arylamines with DNA and have not been readily available by direct synthesis. Ability to generate significant quantities of this class of DNA adduct by synthetic means would facilitate basic research in molecular toxicology. Two routes with common thiourea intermediates were developed for this purpose. In the first route, 6-hydroxy-2,4,5-triaminopyrimidine was caused to react in aqueous medium with dithiocarbamate derivatives of o-, m-, or p-toluidine to form corresponding 2,4-diamino-5-(tolylthioureido)aminopyrimidin-6-ones in 60-70% yields. The thiourea intermediates were converted to carbodiimides and isolated in 20-25% yields after treatment with HgO in dimethylformamide. The carbodiimides were cyclized at 125 degrees C in dimethylformamide under N2 for 45 h to yield N-(guanin-8-yl)(o-, m-, or p-)toluidines in 65-75% yields. In the second route, direct reaction of p-tolyl isothiocyanate with 6-hydroxy-2,4,5-triaminopyrimidine or with 4,5,6-triaminopyrimidine in dimethylformamide and triethylamine led to the formation of 2,4-diamino-5-(p-tolylthioureido)aminopyrimidin-6-one and 4,6-diamino-5-(tolylthioureido)aminopyrimidine, respectively, in 77-79% yields. Methylation of the two thiourea derivatives by methyl iodide in dimethylformamide gave the corresponding methylisothiuronium derivatives, which were isolated in 71% and 84% yields (as HI salts), respectively. Conversion of the methylisothiuronium derivatives to N-(guanin-8-yl)-p-toluidine or N-(adenin-8-yl)-p-toluidine was accomplished by heating in dimethylformamide for 5-7 h at 80-90 degrees C, in 70% and 62% yields, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of N-(purin-8-yl)arylamines

Swenson

El‐Bayoumy

Shuie

et al. 1993

Chem. Res. Toxicol.

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“…Also, most methods perform a targeted analysis, measuring single, or a few, forms of DNA damage simultaneously [ 43 ]. Widely used methods include HPLC–MS/MS [ 44 ], the comet assay (single cell gel electrophoresis) [ 45 , 46 ] and immunochemical methods [ 47 ], such as ELISA [ 48 ]. HPLC–MS/MS is widely regarded as the gold standard approach, providing target identification and absolute quantification.…”

Section: Methods For Measuring Dna Damagementioning

confidence: 99%

Genome-wide mapping of genomic DNA damage: methods and implications

Amente

Scala

Majello

et al. 2021

Cell. Mol. Life Sci.

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Exposures from the external and internal environments lead to the modification of genomic DNA, which is implicated in the cause of numerous diseases, including cancer, cardiovascular, pulmonary and neurodegenerative diseases, together with ageing. However, the precise mechanism(s) linking the presence of damage, to impact upon cellular function and pathogenesis, is far from clear. Genomic location of specific forms of damage is likely to be highly informative in understanding this process, as the impact of downstream events (e.g. mutation, microsatellite instability, altered methylation and gene expression) on cellular function will be positional—events at key locations will have the greatest impact. However, until recently, methods for assessing DNA damage determined the totality of damage in the genomic location, with no positional information. The technique of “mapping DNA adductomics” describes the molecular approaches that map a variety of forms of DNA damage, to specific locations across the nuclear and mitochondrial genomes. We propose that integrated comparison of this information with other genome-wide data, such as mutational hotspots for specific genotoxins, tumour-specific mutation patterns and chromatin organisation and transcriptional activity in non-cancerous lesions (such as nevi), pre-cancerous conditions (such as polyps) and tumours, will improve our understanding of how environmental toxins lead to cancer. Adopting an analogous approach for non-cancer diseases, including the development of genome-wide assays for other cellular outcomes of DNA damage, will improve our understanding of the role of DNA damage in pathogenesis more generally.

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Can a non-tumorigenic dose of carcinogen cause two or more errors in a cell?

Volpe

1992

Cancer Letters

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Measurement of DNA Adducts by Immunoassays

Cited by 3 publications

References 21 publications

Synthesis of N-(purin-8-yl)arylamines

Synthesis of N-(purin-8-yl)arylamines

Genome-wide mapping of genomic DNA damage: methods and implications

Can a non-tumorigenic dose of carcinogen cause two or more errors in a cell?

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