Cu同位素癌症诊断应用潜力研究

Copper (Cu) stable isotopes are a newly developed geochemical tool in tracing metal contamination in the environment. The research on Cu isotopes has grown rapidly in the last decade. Hitherto, a large number of studies have been published on the theoretical fractionation mechanisms, experimental data and natural variations of Cu isotopes in variable environments and ecosystems. These studies reported a large variation of δ 65 Cu ( − 16.49 to +20.04 ‰ ) in terrestrial samples and showed that Cu isotopes could be fractionated by various biogeochemical processes to different extent. Particularly, researchers applied Cu to human health study, and found that as a marker, the δ65Cu decline preceded biomarkers for several months, thus suggested a strong potential of Cu isotope composition as a new diagnostic tool at least for breast and colorectal cancers. However, a series of experimental researches are needed to verify this significant possibility. In this study, we will compare the variations of Cu isotope ratios and blood routine examination results of healthy and cancered Wistar rats of different periods. Furthermore, the results would be extrapolated to human to discuss the potential of Cu isotope being used as a valid and sensitive diagnostic tool for cancer. In this pilot study, we try to use geochemical method in cancer diagnosis, which is of great significance for providing a new application of Cu isotopes.

Cu同位素是国际上新近发展起来的示踪环境重金属污染的有效地球化学研究手段。在过去的十多年里，Cu同位素研究发展迅速。近年来发表的针对不同表层储库、动物以及人体中Cu同位素的研究报道了陆地样品具有较大的δ65Cu变化范围(−16.49~ +20.04‰)，并显示许多生物地球化学过程均可导致不同程度的Cu同位素分馏。值得提出的是，有学者尝试将金属稳定同位素这一地球化学研究手段应用于人体健康研究领域，并发现乳腺癌和结肠直肠癌患者血清中δ65Cu值下降先于医院常规监测的生物指标变化长达数月之久，意味着Cu同位素组成有望作为一种新的乳腺癌和结肠直肠癌的诊断手段。然而，这一重要的发现尚需开展一系列的实验研究来验证。本课题拟开展健康及患癌（肝癌和乳腺癌）不同时期的Wistar大鼠血液的Cu同位素组成及血常规分析，并结合相应的切片分析来探究Cu同位素组成的变化与癌症常规检测的生物指标变化之间的关系，进而外

Cu 同位素是国际上新近发展起来的示踪环境重金属污染的有效地球化学研究手段。有学者尝试将金属稳定同位素这一地球化学研究手段应用于人体健康研究领域，并发现乳腺癌等患者血清中δ65Cu 值下降先于医院常规监测的生物指标变化长达数月之久，意味着 Cu 同位素组成有望作为一种新的癌症诊断手段。为探讨铜同位素在癌症诊断方面的应用潜力，本项目开展了人为诱导的肝癌、乳腺癌动物模型，定期处死大鼠以获得癌变不同阶段的样本，研究结果显示(1)肝癌大鼠血清铜含量变化早于肝功能指标；(2)在肝癌早期血清中铜同位素变化相比于铜含量更为明显，且铜同位素组成较之对照组明显偏负；(3)乳腺癌演进过程中，血清及乳腺组织中铜蓝蛋白变化具有规律性，铜蓝蛋白含量呈上升趋势。本研究是地球化学同位素手段在生物医学方面应用的大胆尝试，因此具有重要现实意义和参考价值。