Linking exposure to environmental stress factors with diseases is crucial for proposing preventive and regulatory actions. Upon exposure to anthropogenic chemicals, covalent modifications on the genome can drive developmental and reproductive disorders in wild populations, with subsequent effects on the population persistence. Hence, screening of chemical modifications on DNA can be used to provide information on the probability of such disorders in populations of concern. Using a high-resolution mass spectrometry methodology, we identified DNA nucleoside adducts in gravid females of the Baltic amphipods Monoporeia affinis, and linked the adduct profiles to the frequency of embryo malformations in the broods. Twenty-three putative nucleoside adducts were detected in the females and their embryos, and eight modifications were structurally identified using high-resolution accurate mass data. To identify which adducts were significantly associated with embryo malformations, partial least squares regression (PLSR) modelling was applied. The PLSR model yielded three adducts as the key predictors: methylation at two different positions of the DNA (5-methyl-2'-deoxycytidine and N6-methyl-2'-deoxyadenosine) representing epigenetic marks, and a structurally unidentified nucleoside adduct. These adducts predicted the elevated frequency of the malformations with a high classification accuracy (84%). To the best of our knowledge, this is the first application of DNA adductomics for identification of contaminant-induced malformations in field-collected animals. The method can be adapted for a broad range of species and evolve as a new omics tool in environmental health assessment.

中文翻译：

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DNA表观遗传标记与两栖动物的胚胎畸变有关。

将环境压力因素的暴露与疾病联系起来对于提出预防和监管措施至关重要。暴露于人为化学物质后，基因组上的共价修饰可导致野生种群的发育和生殖失调，进而对种群的持久性产生影响。因此，对DNA进行化学修饰的筛选可用于提供有关人群中此类疾病发生概率的信息。使用高分辨率质谱方法，我们在波罗的海两栖类单胞菌亲子母的妊娠雌虫中鉴定了DNA核苷加合物，并将该加合物概况与育雏中胚胎畸形的频率联系起来。在雌性和它们的胚胎中发现了二十三个推定的核苷加合物，使用高分辨率的精确质量数据在结构上确定了八种修饰。为了确定哪些加合物与胚胎畸形显着相关，应用了偏最小二乘回归（PLSR）模型。PLSR模型产生了三个加合物作为关键预测因子：代表表观遗传标记的DNA两个不同位置的甲基化（5-甲基-2'-脱氧胞苷和N6-甲基-2'-脱氧腺苷），以及结构上不确定的核苷加合物。这些加合物以较高的分类精度（84％）预测了畸形的发生率。据我们所知，这是DNA原子切割技术在野外采集的动物中识别污染物引起的畸形的首次应用。