摘要
微量金属元素在生命过程中扮演重要角色,其含量和分布由生物系统严格调节,并直接受到外部环境的影响。铜和锌在免疫调节、蛋白质合成和催化反应等方面发挥特定作用,其稳态失衡可能导致氧化应激反应、炎症损伤甚至疾病。研究表明,金属稳定同位素在地质、环境过程中普遍发生分馏,成为环境金属来源的有效示踪手段。而生物新陈代谢过程中,氧化还原反应、配体结合能改变等也会造成明显金属稳定同位素分馏。因此,研究生物体金属稳定同位素的组成、分布与平衡,有助于深入理解金属稳态及相关代谢过程。本文在系统总结了人体铜、锌同位素分布特征,阐述了性别、年龄、饮食习惯和环境暴露等因素对铜、锌同位素分馏影响的基础上,主要总结和讨论了癌症演进过程中人体铜、锌同位素稳态失衡的过程机制。结果表明,在癌症发展过程中,铜和锌同位素除分别受到性别和饮食习惯影响外,癌症患者相对健康人群血液明显富集轻铜同位素,而尿液富集轻锌同位素,展示了金属稳定同位素在癌症诊断和预后方面的巨大潜力。未来,应在标准化样品处理流程的基础上,完善人体金属同位素数据库,明确生命过程金属同位素分馏机理,为金属稳定同位素在临床疾病如癌症中的诊断应用奠定理论基础。
Trace metal elements play crucial roles in biological systems,with their concentrations and distributions being strictly regulated by biological processes and influenced by external environmental factors.Copper and zinc play specific functions in immunoregulation,protein synthesis,and catalytic reactions.Disruptions of these two metals in biological homeostasis can lead to oxidative stress responses,inflammatory damage,and even diseases.The recently-developed isotope approach of these two metals has shown great potential for tracing not only their transformation in various environments,but also during different metabolic processes,as metal stable isotopes primarily fractionate during the changes of redox reactions and ligand binding energies.Therefore,studying the composition,distribution,and balance of metal stable isotopes in various organisms would enhance our understanding of metal homeostasis and related metabolic processes.In this study,copper and zinc isotopes were taken as examples to show the potential of metal stable isotopes for tracing special life processes especially the cancer progression.We first summarized Cu and Zn isotopic compositions in the human body and the relative influence factors such as sex,age,dietary habits,and environmental exposure,and then discussed the imbalance of Cu and Zn isotope homeostasis during cancer progression.Although Cu and Zn isotope ratios in various tissues have been found to be influenced by sex and dietary habits,the significant enrichment of light Cu isotopes in blood and light Zn isotopes in urine of cancer patients compared to the healthy controls during cancer progression highlights the potential of metal stable isotopes in cancer diagnosis and prognosis.In the future,the extended human metal isotope database could help identify the mechanisms of metal isotope fractionation during special metabolic processes such as cancer progression,which would in turn help to explore the potential clinical applications of metal stable isotopes.
作者
刘文奇
王柱红
刘洋
马宁
陈岩
郑旺
刘红
陈玖斌
LIU Wenqi;WANG Zhuhong;LIU Yang;MA Ning;CHEN Yan;ZHENG Wang;LIU Hong;CHEN Jiubin(Institute of Surface-Earth System Science,School of Earth System Science,Tianjin University,Tianjin 300072,China;School of Public Health,The Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,Guiyang 561113,China;Division of Life Science,Hong Kong University of Science and Technology,Hong Kong 999077,China;The Second Department Breast Cancer,Tianjin Medical University Cancer Institute and Hospital,Tianjin 300060,China)
出处
《地学前缘》
北大核心
2025年第3期408-424,共17页
Earth Science Frontiers
基金
国家自然科学基金项目(42421003)。
关键词
铜
锌
金属稳定同位素
癌症
copper
zinc
metal stable isotopes
cancer
