Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100083, China.
School of Engineering Medicine and Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing 100083, China.
J Environ Sci (China). 2025 May;151:150-160. doi: 10.1016/j.jes.2024.01.054. Epub 2024 Feb 12.
Toxic effects in terms of mitochondria and hereditary substances have been characterized in vitro for individual rare earth elements, while, the joint effects of mixed elements exposure in the population remain ambiguous. Based on the Occupational Chromate Exposure Dynamic Cohort of China, this study investigated the relationship between 15 blood rare earth elements (cerium, dysprosium, erbium, europium, gadolinium, holmium, lanthanum, lutetium, neodymium, praseodymium, samarium, terbium, thulium, yttrium, and ytterbium) and mitochondrial DNA copy number (MtDNACN) as well as peripheral blood lymphocyte micronucleus frequency (MNF). The elastic net was used to select elements highly correlated with effect indicators, whose dose-response relationships were further illustrated by restricted cubic splines. Bayesian kernel regression was employed to explore the combined effects of elements and the contributions of single element. The results showed that most rare earth elements were positively correlated with effect indicators, with yttrium showing the strongest association (β (95% CI): 0.139 (0.1089 - 0.189) for MtDNACN, 0.937 (0.345 - 1.684) for MNF). In the mixed exposure model, with the exposure level fixed at the 50th percentile as the reference, the effect estimates on MtDNACN and MNF increased by 0.228 and 0.598 units, respectively, at the 75th percentile. The single effect analysis implied that yttrium, lanthanum and terbium contributed the most to the elevation of MtDNACN, while yttrium posed the highest risk for genetic damage, accordingly, we provided recommendations to prioritize these elements of concern. In addition, we observed a chief mediating effect of MtDNACN on the elevation of MNF caused by lanthanum, whereas further mechanistic exploration is required to confirm this finding.
在体外，已经对个别稀土元素的线粒体和遗传物质毒性作用进行了研究，而人群中混合元素暴露的联合效应仍不清楚。本研究基于中国职业铬暴露动态队列，调查了 15 种血液稀土元素（铈、镝、铒、铕、钆、钬、镧、镥、钕、镨、钐、铽、铥、钇和镱）与线粒体 DNA 拷贝数（MtDNACN）以及外周血淋巴细胞微核频率（MNF）之间的关系。弹性网络用于选择与效应指标高度相关的元素，通过限制立方样条进一步说明其剂量-反应关系。贝叶斯核回归用于探索元素的联合效应及其单个元素的贡献。结果表明，大多数稀土元素与效应指标呈正相关，其中钇的相关性最强（MtDNACN 的β（95%置信区间）：0.139（0.1089-0.189），MNF 的β：0.937（0.345-1.684））。在混合暴露模型中，将暴露水平固定在第 50 百分位作为参考，第 75 百分位时，MtDNACN 和 MNF 的效应估计值分别增加了 0.228 和 0.598 个单位。单一效应分析表明，钇、镧和铽对 MtDNACN 的升高贡献最大，而钇对遗传损伤的风险最高，因此，我们建议优先考虑这些关注元素。此外，我们观察到镧引起的 MNF 升高与 MtDNACN 之间存在主要的中介效应，然而，需要进一步的机制探索来证实这一发现。
