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不同光谱组成的夜间人造光对小鼠肿瘤生长有不同影响:与褪黑素及表观遗传途径的相互作用

Artificial Light at Night of Different Spectral Compositions Differentially Affects Tumor Growth in Mice: Interaction With Melatonin and Epigenetic Pathways.

作者信息

Zubidat A E, Fares B, Fares F, Haim A

机构信息

1 The Israeli Center for Interdisciplinary Research in Chronobiology, University of Haifa, Haifa, Israel.

2 Department of Human Biology, University of Haifa, Haifa, Israel.

出版信息

Cancer Control. 2018 Jan-Dec;25(1):1073274818812908. doi: 10.1177/1073274818812908.

Abstract

Lighting technology is rapidly advancing toward shorter wavelength illuminations that offer energy-efficient properties. Along with this advantage, the increased use of such illuminations also poses some health challenges, particularly breast cancer progression. Here, we evaluated the effects of artificial light at night (ALAN) of 4 different spectral compositions (500-595 nm) at 350 Lux on melatonin suppression by measuring its urine metabolite 6-sulfatoxymelatonin, global DNA methylation, tumor growth, metastases formation, and urinary corticosterone levels in 4T1 breast cancer cell-inoculated female BALB/c mice. The results revealed an inverse dose-dependent relationship between wavelength and melatonin suppression. Short wavelength increased tumor growth, promoted lung metastases formation, and advanced DNA hypomethylation, while long wavelength lessened these effects. Melatonin treatment counteracted these effects and resulted in reduced cancer burden. The wavelength suppression threshold for melatonin-induced tumor growth was 500 nm. These results suggest that short wavelength increases cancer burden by inducing aberrant DNA methylation mediated by the suppression of melatonin. Additionally, melatonin suppression and global DNA methylation are suggested as promising biomarkers for early diagnosis and therapy of breast cancer. Finally, ALAN may manifest other physiological responses such as stress responses that may challenge the survival fitness of the animal under natural environments.

摘要

照明技术正迅速朝着具有节能特性的更短波长照明发展。伴随着这一优势,此类照明的使用增加也带来了一些健康挑战,尤其是乳腺癌进展方面。在此,我们通过测量4T1乳腺癌细胞接种的雌性BALB/c小鼠尿液中的褪黑素代谢物6-硫酸氧褪黑素、全基因组DNA甲基化、肿瘤生长、转移形成以及尿皮质酮水平,评估了350勒克斯下4种不同光谱组成(500 - 595纳米)的夜间人工光(ALAN)对褪黑素抑制的影响。结果显示波长与褪黑素抑制之间存在剂量反比关系。短波长增加肿瘤生长、促进肺转移形成并加剧DNA低甲基化,而长波长则减轻了这些影响。褪黑素治疗抵消了这些影响并减轻了癌症负担。褪黑素诱导肿瘤生长的波长抑制阈值为500纳米。这些结果表明,短波长通过抑制褪黑素介导的异常DNA甲基化增加癌症负担。此外,褪黑素抑制和全基因组DNA甲基化被认为是乳腺癌早期诊断和治疗的有前景的生物标志物。最后,夜间人工光可能表现出其他生理反应,如应激反应,这可能会挑战动物在自然环境中的生存适应性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7246/6259078/c464a9ad4f5f/10.1177_1073274818812908-fig1.jpg

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