Trophic transfer of carbon-14 from algae to zebrafish leads to its blending in biomolecules and the dysregulation of metabolism via isotope effect.

IF 16.3 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES National Science Review Pub Date : 2024-09-30 eCollection Date: 2025-01-01 DOI:10.1093/nsr/nwae346
Shipeng Dong, Renquan Deng, Hang Zeng, Pengfei Xue, Sijie Lin, Dongmei Zhou, Liang Mao
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Abstract

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 (Scenedesmus obliquus), daphnia (Daphnia magna) and zebrafish (Danio rerio), 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 12C/14C 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.

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碳-14从藻类向斑马鱼的营养转移导致其生物分子混合,并通过同位素效应导致代谢失调。
碳-14 (C-14)一直是人类放射性暴露剂量的主要来源,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)的形式进入生物圈,对公众健康构成潜在威胁。然而,尚不清楚这种放射性毒性相对较低的核素如何通过同位素效应等化学效应引起健康风险。通过建立藻类(Scenedesmus obliquus)、水蚤(daphnia magna)和斑马鱼(Danio rerio)的营养转移模型,我们发现藻类将无机碳-14快速结合并转化为OBC-14,促进了碳-14与斑马鱼生物分子的混合。我们发现内化的C-14持续保留在斑马鱼的大脑中,影响DNA甲基化并引起神经病理学的改变。碳-14暴露的全球同位素示踪代谢组学进一步揭示了碳-14参与多种关键代谢途径,包括单碳代谢和核苷酸代谢。因此,我们通过动力学实验和密度功能理论计算表征了12C/14C在这些代谢途径的关键反应中的动力学同位素效应,表明生物化学中碳的同位素取代通过同位素效应破坏反应比率来调节代谢。我们的研究结果表明,核工业排放的无机C-14可以通过同位素效应生物转化为OBC-14,从而影响代谢,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。
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来源期刊
National Science Review
National Science Review MULTIDISCIPLINARY SCIENCES-
CiteScore
24.10
自引率
1.90%
发文量
249
审稿时长
13 weeks
期刊介绍: National Science Review (NSR; ISSN abbreviation: Natl. Sci. Rev.) is an English-language peer-reviewed multidisciplinary open-access scientific journal published by Oxford University Press under the auspices of the Chinese Academy of Sciences.According to Journal Citation Reports, its 2021 impact factor was 23.178. National Science Review publishes both review articles and perspectives as well as original research in the form of brief communications and research articles.
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