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.

化学污染的暴露可能导致遗传和表观遗传的改变、发育异常以及生殖障碍，进而导致污染环境中种群数量的下降。此类效应源于DNA碱基（DNA加合物）的化学修饰以及表观遗传的失调。然而，将DNA加合物与现场污染负荷相联系仍是一项挑战，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。在本研究中，我们首次提供了污染对波罗的海哨兵物种——沼虾Monoporeia affinis野生种群DNA修饰的影响证据。开发了一种基于高分辨率质谱的工作流程，用于筛选和表征基因组DNA修饰，并通过分析在不同污染负荷区域收集的沼虾中的DNA修饰来验证其适用性。随后，评估了加合物与采集地点沉积物中污染物水平（多环芳烃（PAHs）、微量元素和污染指数）之间的相关性。共检测到119个潜在的加合物，其中一些（5-甲基-dC、N6-甲基-dA、8-氧代-dG和dI）进行了结构表征。DNA加合物库的配置文件，包括表观遗传修饰，在高污染水平和低污染水平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，表明可能存在累加效应。与低质量加合物相比，高质量加合物与PAHs的相关性显著更正。相反，DNA加合物与微量元素的相关性比PAHs更强且变化更大，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以及将DNA修饰应用于基于效果的化学污染评估提供了一个新的途径。