Assessment of variability in the human urinary nucleic acid adductome
Abstract
Assessment of the urinary nucleic acid adductome provides a valuable, non-invasive approach for evaluating whole-body exposure to genotoxins. To support its application to exposome research, a clear understanding of biological variability independent of exposure is required. In this study, we analyzed a urine biobank from 40 healthy, non-smoking adults. Samples were processed using dual-phase solid-phase extraction, which retains a broad spectrum of nucleic acid adducts, and analyzed using an Orbitrap IQX platform. Data processing was performed using MZmine, FeatureHunter, and MetaboAnalyst. Across approximately 160 adducts per sample, the number of recovered adducts remained consistent between collection times, indicating that qualitative characterization of the urinary nucleic acid adductome is largely unaffected by diurnal variation. Most adducts exhibited stable abundances across sampling times. Diurnal variation was observed only in males, with 10 adducts showing significant differences between collection times, while females showed no temporal differences. Of the total adducts detected, only 32 differed significantly by age and/or sex. Age-related differences were more pronounced, particularly in males, where all significantly altered adducts were present at higher intensities in the younger cohort (20 to 29 y) compared with the older cohort (30 to 60 y). These findings support the use of spot urine samples for adductomic studies, favoring first-void urine. Collectively, these findings provide the first comprehensive assessments of biological variability within the human urinary nucleic acid adductome and support its application as a robust biomonitoring tool for investigating endogenous and environmental exposures across diverse human populations.
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BibTeX
@misc{keidel2026assessment,
title = {{Assessment of variability in the human urinary nucleic acid adductome}},
author = {Alexandra Keidel and Jazmine Virzi and Mina Mckee and Yuan-Jhe Chang and Mu-Rong Chao and Chiung-Wen Hu and Leo Stockfelt and Gerd Sallsten and Lars Barregard and Marcus S. Cooke},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.14.759185},
url = {https://www.biorxiv.org/content/10.64898/2026.10.14.759185v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Assessment of variability in the human urinary nucleic acid adductome
AU - Alexandra Keidel
AU - Jazmine Virzi
AU - Mina Mckee
AU - Yuan-Jhe Chang
AU - Mu-Rong Chao
AU - Chiung-Wen Hu
AU - Leo Stockfelt
AU - Gerd Sallsten
AU - Lars Barregard
AU - Marcus S. Cooke
PY - 2026
DA - 2026/10/14
PB - bioRxiv
DO - 10.64898/2026.10.14.759185
UR - https://www.biorxiv.org/content/10.64898/2026.10.14.759185v1
AB - Assessment of the urinary nucleic acid adductome provides a valuable, non-invasive approach for evaluating whole-body exposure to genotoxins. To support its application to exposome research, a clear understanding of biological variability independent of exposure is required. In this study, we analyzed a urine biobank from 40 healthy, non-smoking adults. Samples were processed using dual-phase solid-phase extraction, which retains a broad spectrum of nucleic acid adducts, and analyzed using an Orbitrap IQX platform. Data processing was performed using MZmine, FeatureHunter, and MetaboAnalyst. Across approximately 160 adducts per sample, the number of recovered adducts remained consistent between collection times, indicating that qualitative characterization of the urinary nucleic acid adductome is largely unaffected by diurnal variation. Most adducts exhibited stable abundances across sampling times. Diurnal variation was observed only in males, with 10 adducts showing significant differences between collection times, while females showed no temporal differences. Of the total adducts detected, only 32 differed significantly by age and/or sex. Age-related differences were more pronounced, particularly in males, where all significantly altered adducts were present at higher intensities in the younger cohort (20 to 29 y) compared with the older cohort (30 to 60 y). These findings support the use of spot urine samples for adductomic studies, favoring first-void urine. Collectively, these findings provide the first comprehensive assessments of biological variability within the human urinary nucleic acid adductome and support its application as a robust biomonitoring tool for investigating endogenous and environmental exposures across diverse human populations.
SN - 2692-8205
ER -