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Determination of N7-glycidamide guanine adducts in human blood DNA following exposure to dietary acrylamide using liquid chromatography/tandem mass spectrometry

journal contribution
posted on 2022-02-16, 07:14 authored by Donald JL Jones, Raj Singh, Victoria Emms, Peter B Farmer, Derryn Grant, Paulene Quinn, Colleen Maxwell, Antria Mina, Leong L Ng, Sandra Schumacher, Robert G Britton
Rationale
Acrylamide is classified as a probable human carcinogen that is metabolised to glycidamide, which can covalently bind to DNA. The aim of this study was to investigate the formation of N7-glycidamide guanine (N7-GA-Gua) adducts in human blood DNA following exposure to acrylamide present in carbohydrate-rich foods as part of the normal human diet.

Methods
Lymphocyte DNA was extracted from blood samples obtained from healthy human volunteers. Following thermal depurination of the DNA samples, N7-GA-Gua adducts were quantified using a validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method incorporating a stable isotope labelled internal standard. Estimated dietary acrylamide intake was recorded by completion of food frequency questionnaires for the 24 hours prior to volunteer blood donation.

Results
An LC/MS/MS method was validated with a limit of detection of 0.25 fmol and a lower limit of quantitation of 0.50 fmol on column. N7-GA-Gua adducts were detected in human blood DNA with the levels ranging between 0.3 to 6.3 adducts per 108 nucleotides. The acrylamide intake was calculated from the food frequency questionnaires ranging between 20.0 and 78.6 μg.

Conclusions
Identification and quantification of N7-GA-Gua adducts in the blood DNA of healthy volunteers suggests that dietary acrylamide exposure may lead to the formation of DNA adducts. This important finding warrants further investigation to ascertain a correlation between environmental/dietary acrylamide exposure and levels of DNA adducts.

Funding

World Cancer Research Fund

History

Citation

Rapid Communications in Mass Spectrometry, Volume 36, Issue 6, 30 March 2022, e9245

Author affiliation

Leicester Cancer Research Centre, University of Leicester

Version

  • AM (Accepted Manuscript)

Published in

Rapid Communications in Mass Spectrometry

Volume

36

Issue

6

Publisher

Wiley

issn

0951-4198

eissn

1097-0231

Acceptance date

2021-12-15

Copyright date

2021

Available date

2022-12-22

Language

en

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