The Effect of n-6 Polyunsaturated Fatty Acid on Blood Levels of Malondialdehyde-Deoxyguanosine Adducts in Human Subjects

Moore, Sharon A.; Humphreys, Emma; Friesen,; Shuker, David E. G.; Bingham, Sheila

doi:10.2174/1875318300801010028

Cited by 3 publications

(6 citation statements)

References 27 publications

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“…The analysis of blood samples is particularly relevant for biomonitoring studies if they are to be as non-invasive as possible. The results for M 1 dG in colorectal mucosa samples from the EPIC study had been previously reported and a weak correlation was found with dietary saturated fat (18) which was corroborated in an intervention study using blood samples (22). The corresponding EPIC blood samples have now been analysed and the results are reported in this paper.…”

Section: Introductionsupporting

confidence: 76%

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Optimizing immunoslot blot assays and application to low DNA adduct levels using an amplification approach

Moore

Xeniou

Zeng

et al. 2010

Analytical Biochemistry

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Immunoslot blot assays have been used for the analysis of many DNA adducts but problems are frequently encountered in achieving reproducible results. Each step of the assay has been systematically examined and it was found that the major problems are in the DNA fragmentation step and the use of the manifold apparatus. Optimisation was performed upon both the malondialdehyde-deoxyguanosine adduct (M 1 dG) and the O 6 -carboxymethyldeoxyguanosine adduct (O 6 CMdG) to demonstrate the applicability to other DNA adducts.Blood samples from the EPIC study (n = 162) were analysed for M 1 dG adducts and the data showed no correlation with adduct levels in other tissues indicating that the EPIC blood samples were not useful for studying M 1 dG adducts. Blood samples from a processed meat vs vegetarian diet intervention (n = 6) were analysed for O 6 CMdG and many were below the limit of detection. The reduction of background adduct levels in standard DNA was investigated using chemical and whole-genome amplification approaches. The latter gave a sensitivity improvement of 2.6 adducts per 10 7 nucleotides for the analysis of O 6 CMdG.Subsequent reanalysis for O 6 CMdG showed a weakly significant increase in O 6 CMdG on the processed meat diet compared with the vegetarian diet, demonstrating that further studies are warranted.

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Section: Introductionsupporting

confidence: 76%

“…However, an intervention study had demonstrated the importance of taking samples at appropriate time points (22).…”

Section: O 6 Cmdg Adducts In Blood Samples From a Processed Meat Studymentioning

confidence: 99%

Optimizing immunoslot blot assays and application to low DNA adduct levels using an amplification approach

Moore

Xeniou

Zeng

et al. 2010

Analytical Biochemistry

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“…M 1 dG adducts have been positively associated with smoking, alcohol . and diets high in saturated fatty acids . However, there is still ambiguity between studies with associations not always being found.…”

mentioning

confidence: 99%

“…It is known to be mutagenic in bacterial [3] and mammalian cells, [4] and enhances DNA damage caused by some chemicals. [5] Lifestyle factors such as smoking, [6][7][8][9] high fat diets [2,[10][11][12] and alcohol [1] have been associated with increased MDA levels and there is a vast body of evidence that links these to many types of cancer including, but not limited to, lung, breast and colorectal cancers. [13] Thus, MDA is widely used as a marker of oxidative stress and potential disease risk.…”

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confidence: 99%

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Quantitative analysis of malondialdehyde‐guanine adducts in genomic DNA samples by liquid chromatography/tandem mass spectrometry

Yates

Dempster

Murphy

et al. 2017

Rapid Comm Mass Spectrometry

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A fast reliable sample preparation method was used to release adducts in the base form rather than the nucleoside. The methods were optimised to selectively analyse the adducts in the presence of other DNA bases without the need for further sample clean-up. Analysis of genomic DNA gave results consistent with previous work and was applied to new samples. Thus, the method is suitable for the analysis of M (d)G adducts in biological samples. Copyright © 2017 John Wiley & Sons, Ltd.

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Exocycilic DNA Adducts in a Murine Model of Non-alcoholic Steatohepatitis

et al. 2014

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Introduction:Non-alcoholic fatty liver disease is the most common hepatic disorder in Western countries. The transition from abnormal accumulation of lipids toward non-alcoholic steatohepatitis (NASH) represents a key step in the development of chronic liver pathologies. Oxidative stress and lipid peroxidation have often been proposed as mechanisms in the progression to steatohepatitis.Methods:We have examined the hepatic levels of exocyclic DNA adducts, indicated from 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adduct, a biomarker of oxidative stress and lipid peroxidation, in a murine model of NASH using the 32P-DNA postlabeling assay.Results:Our findings show that C57BL/6 mice fed with high-fat and cholesterol diet developed signs associated with NASH after eight weeks, whereas there was no evidence of steatosis in control mice. The score for steatohepatitis ranged from grade 2 to 3 for steatosis, inflammation, and fibrosis, showing that the experimental diet was able to induce pathologic alterations of the parenchyma in eight weeks. Higher levels of M1dG adducts were detected in the livers of C57BL/6 mice which developed experimental NASH after eight weeks of high-fat and cholesterol feed, 5.6 M 1dG ± 0.4 (SE) per 106 total nucleotides, as compared to control mice, 1.6 M1dG ± 0.4 (SE). The statistical analysis showed that the increment of oxidatively damaged DNA in mice with NASH raised on high-fat and cholesterol diet was statistically significant as compared to control mice, P=0.006.Conclusions:Our report suggests a link between NASH and M1dG in experimental animals fed with a diet rich in saturated fats and cholesterol. High-fat and cholesterol may act together in inducing a broader spectrum of oxidatively damaged DNA, including exocyclic DNA adducts, that may contribute to the decline of hepatocyte functions, from disturbance of critical pathways, such as transcription and replication, triggering transient or permanent cell-cycle arrest and cell-death, up to chromosomal instability.

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The Effect of n-6 Polyunsaturated Fatty Acid on Blood Levels of Malondialdehyde-Deoxyguanosine Adducts in Human Subjects

Cited by 3 publications

References 27 publications

Optimizing immunoslot blot assays and application to low DNA adduct levels using an amplification approach

Optimizing immunoslot blot assays and application to low DNA adduct levels using an amplification approach

Quantitative analysis of malondialdehyde‐guanine adducts in genomic DNA samples by liquid chromatography/tandem mass spectrometry

Exocycilic DNA Adducts in a Murine Model of Non-alcoholic Steatohepatitis

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