Dong Shipeng, Deng Renquan, Zeng Hang, Xue Pengfei, Lin Sijie, Zhou Dongmei, Mao Liang
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210023, China.
College of Environmental Science & Engineering, State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, Shanghai 200092, China.
Natl Sci Rev. 2024 Sep 30;12(1):nwae346. doi: 10.1093/nsr/nwae346. eCollection 2025 Jan.
Carbon-14 (C-14) has been a major contributor to the human radioactive exposure dose, as it is released into the environment from the nuclear industry in larger quantities compared to other radionuclides. This most abundant nuclide enters the biosphere as organically bound C-14 (OBC-14), posing a potential threat to public health. Yet, it remains unknown how this relatively low radiotoxic nuclide induces health risks via chemical effects, such as isotope effect. By establishing a trophic transfer model involving algae (), daphnia () and zebrafish (), we demonstrate that rapid incorporation and transformation of inorganic C-14 by algae into OBC-14 facilitates the blending of C-14 into the biomolecules of zebrafish. We find that internalized C-14 is persistently retained in the brain of zebrafish, affecting DNA methylation and causing alterations in neuropathology. Global isotope tracing metabolomics with C-14 exposure further reveals the involvement of C-14 in various critical metabolic pathways, including one-carbon metabolism and nucleotide metabolism. We thus characterize the kinetic isotope effects for C/C in the key reactions of these metabolic pathways through kinetic experiments and density functional theory computations, showing that the isotopic substitution of carbon in biochemicals regulates metabolism by disrupting reaction ratios via isotope effects. Our results suggest that inorganic C-14 discharged by the nuclear industry can be biotransformed into OBC-14 to impact metabolism via isotope effects, providing new insights into understanding the health risk of C-14, which is traditionally considered as a low radiotoxic nuclide.
碳 - 14（C - 14）一直是人类放射性暴露剂量的主要贡献者，因为与其他放射性核素相比，它从核工业释放到环境中的量更大。这种最丰富的核素以有机结合的C - 14（OBC - 14）形式进入生物圈，对公众健康构成潜在威胁。然而，这种相对低放射性毒性的核素如何通过化学效应（如同位素效应）引发健康风险仍不清楚。通过建立一个涉及藻类（ ）、水蚤（ ）和斑马鱼（ ）的营养转移模型，我们证明藻类将无机C - 14快速纳入并转化为OBC - 14，促进了C - 14融入斑马鱼的生物分子中。我们发现内化的C - 14持续保留在斑马鱼的大脑中，影响DNA甲基化并导致神经病理学改变。C - 14暴露的全同位素示踪代谢组学进一步揭示了C - 14参与各种关键代谢途径，包括一碳代谢和核苷酸代谢。因此，我们通过动力学实验和密度泛函理论计算表征了这些代谢途径关键反应中C/C的动力学同位素效应，表明生物化学物质中碳的同位素取代通过同位素效应破坏反应比例来调节代谢。我们的结果表明，核工业排放的无机C - 14可以生物转化为OBC - 14，通过同位素效应影响代谢，为理解传统上被认为是低放射性毒性核素的C - 14的健康风险提供了新的见解。
