We investigated whether exposure to carcinogenic diesel engine exhaust (DEE) was associated with altered adduct levels in human serum albumin (HSA) residues. Nano-liquid chromatography-high resolution mass spectrometry (nLC-HRMS) was used to measure adducts of Cys34 and Lys525 residues in plasma samples from 54 diesel engine factory workers and 55 unexposed controls. An untargeted adductomics and bioinformatics pipeline was used to find signatures of Cys34/Lys525 adductome modifications. To identify adducts that were altered between DEE-exposed and unexposed participants, we used an ensemble feature selection approach that ranks and combines findings from linear regression and penalized logistic regression, then aggregates the important findings with those determined by random forest. We detected 40 Cys34 and 9 Lys525 adducts. Among these findings, we found evidence that 6 Cys34 adducts were altered between DEE-exposed and unexposed participants (i.e., 841.75, 851.76, 856.10, 860.77, 870.43, and 913.45). These adducts were biologically related to antioxidant activity.

我们研究了暴露于致癌柴油发动机废气 (DEE) 是否与人血清白蛋白 (HSA) 残留物中加合物水平的改变有关。采用纳米液相色谱-高分辨率质谱 (nLC-HRMS) 测定了 54 名柴油发动机工厂工人和 55 名未暴露对照者血浆样本中 Cys34 和 Lys525 残留物的加合物。使用非靶向加合组学和生物信息学流程来寻找 Cys34/Lys525 加合组修饰的特征。为了识别暴露于 DEE 的参与者和未暴露于 DEE 的参与者之间发生改变的加合物，我们使用了一种集成特征选择方法，该方法对线性回归和惩罚逻辑回归的结果进行排序和组合，然后将重要的发现与随机森林确定的结果进行汇总。我们检测到 40 个 Cys34 和 9 个 Lys525 加合物。在这些发现中，我们发现有证据表明，暴露于 DEE 和未暴露于 DEE 的参与者之间有 6 个 Cys34 加合物发生了改变（即 841.75、851.76、856.10、860.77、870.43 和 913.45）。这些加合物在生物学上与抗氧化活性相关。