Comparison of UV, Fluorescence, and Electrochemical Detectors for the Analysis of Formaldehyde-Induced DNA Adducts

Zhong, Weiguang; Hee, Shane S. Que

doi:10.1093/jat/29.3.182

Cited by 8 publications

(7 citation statements)

References 21 publications

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“…Previous studies show that N 6 -hydroxymethyl-dA is a primary formaldehyde-induced DNA monoadduct. − Surprisingly, our data did not support the formation of detectable amounts of [ 13 CD 2 ]- N 6 -hydroxymethyl-dA from exogenous formaldehyde in cell culture. The detection limit of N 6 -methyl-dA was more sensitive than that of N 2 -methyl-dG, so a lack of sensitivity does not account for our inability to detect exogenous [ 13 CD 2 ]- N 6 -hydroxymethyl-dA.…”

Section: Discussioncontrasting

confidence: 92%

“…Several previous in vitro studies have shown that N 6 -hydroxymethyl-dA is a primary formaldehyde-DNA monoadduct. − Here, we examined the possible formation of N 6 -hydroxymethyl-dA in cells exposed to different doses of formaldehyde, as shown in Figure . Figure A and B gives the LC-ESI-MS/MS-SRM chromatograms of N 2 -methyl-dG in cells exposed to 0.5 mM or 1 mM [ 13 CD 2 ]-formaldehyde for 3 h, while Figure C and D shows the typical chromatograms of N 6 -methyl-dA in cells.…”

Section: Resultsmentioning

confidence: 99%

“…Previous research has demonstrated that formaldehyde is genotoxic in a variety of test systems, causing mutations in multiple genes. − DNA adducts play an important role in mutagenesis and carcinogenesis. The structures of formaldehyde-induced DNA adducts in vitro have been known for decades. − Formaldehyde can typically result in N 6 -hydroxymethyl-dA, N 2 -hydroxymethyl-dG and N 4 -hydroxymethyl-dC in vitro . − Hydroxymethyl DNA adducts arising from formaldehyde are not stable and need to be reduced to their methyl forms for robust quantitation. However, alkylation is another type of DNA damage in cells, with methyl adducts being induced by a variety of alkylating agents.…”

Section: Introductionmentioning

confidence: 99%

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Use of LC-MS/MS and Stable Isotopes to Differentiate Hydroxymethyl and Methyl DNA Adducts from Formaldehyde and Nitrosodimethylamine

Lü

Sessaly

Nakamura

et al. 2012

Chem. Res. Toxicol.

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Formaldehyde is a known human and animal carcinogen that forms DNA adducts, and causes mutations. While there is widespread exposure to formaldehyde in the environment, formaldehyde is also an essential biochemical in all living cells. The presence of both endogenous and exogenous sources of formaldehyde makes it difficult to develop exposure-specific DNA biomarkers. Furthermore, chemicals such as nitrosodimethylamine form one mole of formaldehyde for every mole of methylating agent, raising questions about potential co-carcinogenesis. Formaldehyde-induced hydroxymethyl DNA adducts are not stable and need to be reduced to stable methyl adducts for detection, which adds another layer of complexity to identifying the origins of these adducts. In this study, highly sensitive mass spectrometry methods and isotope labeled compounds were used to differentiate between endogenous and exogenous hydroxymethyl and methyl DNA adducts. We demonstrate that N2-hydroxymethyl-dG is the primary DNA adduct formed in cells following formaldehyde exposure. In addition, we show that alkylating agents induce methyl adducts at N2-dG and N6-dA positions, which are identical to the reduced forms of hydroxymethyl adducts arising from formaldehyde. The use of highly sensitive LC-MS/MS and isotope labeled compounds for exposure solves these challenges and provides mechanistic insights on the formation and role of these DNA adducts.

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Section: Discussioncontrasting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Use of LC-MS/MS and Stable Isotopes to Differentiate Hydroxymethyl and Methyl DNA Adducts from Formaldehyde and Nitrosodimethylamine

Lü

Sessaly

Nakamura

et al. 2012

Chem. Res. Toxicol.

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“…It seems likely that oxidation of morphine takes place at the phenolic oxygen at position 3, making it electrochemically active. This means that it is possible to use HPLC-EC, which usually has a higher sensitivity for some drugs (17), including morphine. In this study, a solid phase extraction method was used for morphine.…”

Section: Discussionmentioning

confidence: 99%

Rapid and sensitive quantitation of morphine using HPLC with electrochemical detection

Mashayekhi

Ghandforoush-Sattari

Hain

2008

Journal of Clinical Pharmacy and Therapeutics

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“…The structures of formaldehyde-induced DNA adducts in vitro have been known for decades [93–96] and include the unstable DNA adducts N 2 -hydroxymethyl-deoxyguanosine ( N 2 -HOMe-dG), N 6 -hydroxymethyl-deoxyadenosine ( N 6 -HOMe-dA), and N 4 -hydroxymethyl-deoxycytosine ( N 4 -HOMe-dC) [118–120]. N 2 -HOMe-dG is the main DNA mono-adduct induced by inhaled formaldehyde, which together with DNA protein crosslinks and toxicity-induced cell proliferation are thought to play important roles in mutagenesis and carcinogenesis.…”

Section: Formaldehydementioning

confidence: 99%

The endogenous exposome

et al. 2014

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The concept of the Exposome, is a compilation of diseases and one’s lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the Endogenous Exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions.

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Comparison of UV, Fluorescence, and Electrochemical Detectors for the Analysis of Formaldehyde-Induced DNA Adducts

Cited by 8 publications

References 21 publications

Use of LC-MS/MS and Stable Isotopes to Differentiate Hydroxymethyl and Methyl DNA Adducts from Formaldehyde and Nitrosodimethylamine

Use of LC-MS/MS and Stable Isotopes to Differentiate Hydroxymethyl and Methyl DNA Adducts from Formaldehyde and Nitrosodimethylamine

Rapid and sensitive quantitation of morphine using HPLC with electrochemical detection

The endogenous exposome

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