DNA Adductomics for the Biological Effect Assessment of Contaminant Exposure in Marine Sediments

Exposure to chemical pollution can induce genetic and
epigenetic
alterations, developmental changes, and reproductive disorders, leading
to population declines in polluted environments. These effects are
triggered by chemical modifications of DNA nucleobases (DNA adducts)
and epigenetic dysregulation. However, linking DNA adducts to the
pollution load in situ remains challenging, and the
lack of evidence-based DNA adductome response to pollution hampers
the development and application of DNA adducts as biomarkers for environmental
health assessment. Here, we provide the first evidence for pollution
effects on the DNA modifications in wild populations of Baltic sentinel
species, the amphipod Monoporeia affinis. A workflow based on high-resolution mass spectrometry to screen
and characterize genomic DNA modifications was developed, and its
applicability was demonstrated by profiling DNA modifications in the
amphipods collected in areas with varying pollution loads. Then, the
correlations between adducts and the contaminants level (polycyclic
aromatic hydrocarbons (PAHs), trace metals, and pollution indices)
in the sediments at the collection sites were evaluated. A total of
119 putative adducts were detected, and some (5-me-dC, N6-me-dA, 8-oxo-dG, and dI) were structurally characterized. The DNA
adductome profiles, including epigenetic modifications, differed between
the animals collected in areas with high and low contaminant levels.
Furthermore, the correlations between the adducts and PAHs were similar
across the congeners, indicating possible additive effects. Also,
high-mass adducts had significantly more positive correlations with
PAHs than low-mass adducts. By contrast, correlations between the
DNA adducts and trace metals were stronger and more variable than
for PAHs, indicating metal-specific effects. These associations between
DNA adducts and environmental contaminants provide a new venue for
characterizing genome-wide exposure effects in wild populations and
apply DNA modifications in the effect-based assessment of chemical
pollution.

化学污染的暴露可引发遗传和表观遗传的变异、发育改变以及生殖障碍，从而导致污染环境中种群数量的减少。此类效应由DNA碱基（DNA加合物）的化学修饰和表观遗传调控异常所触发。然而，将DNA加合物与现场污染负荷相关联仍然具有挑战性，而缺乏基于证据的DNA加合物库对污染的反应证据，阻碍了DNA加合物作为环境健康评估生物标志物的发展和应用。在此，我们首次提供了污染对波罗的海哨兵物种——宽鳍异足虾Monoporeia affinis野生种群DNA修饰的影响的证据。基于高分辨率质谱技术，我们开发了一种工作流程，用于筛选和表征基因组DNA的修饰，并通过在污染负荷不同的区域收集的异足虾样本中分析DNA修饰，证明了其适用性。随后，评估了加合物与收集地点沉积物中污染物水平（多环芳烃（PAHs）、痕量金属和污染指数）之间的相关性。共检测到119个可能的加合物，其中一些（5-甲基-dC、N6-甲基-dA、8-氧代-dG和dI）在结构上进行了表征。DNA加合物库的配置文件，包括表观遗传修饰，在收集地污染水平高和低的区域收集的动物之间存在差异。此外，加合物与PAHs之间的相关性在同类物中相似，表明可能存在加性效应。与低质量加合物相比，高质量加合物与PAHs的正相关性显著更高。相比之下，DNA加合物与痕量金属之间的相关性比PAHs更强且更不稳定，表明存在金属特异性效应。这些DNA加合物与环境污染物的关联为描述野生种群的全基因组暴露效应提供了新的途径，并将DNA修饰应用于基于效果的化学污染评估。