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砷化合物:在急性早幼粒细胞白血病和致癌毒理学中的广泛应用及作用机制。

Arsenic compounds: The wide application and mechanisms applied in acute promyelocytic leukemia and carcinogenic toxicology.

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.

出版信息

Eur J Med Chem. 2021 Oct 5;221:113519. doi: 10.1016/j.ejmech.2021.113519. Epub 2021 May 4.

Abstract

Arsenic (As), as well as its various compounds have been widely used for nearly 4000 years either as drugs or poisons. These compounds are valuable in the treatment of various diseases ranging from dermatosis to cancer, thereby emphasizing their important roles as therapeutic agents. The ability of As compounds, especially arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL), has fundamentally altered people's understanding of the poison, and has become a major factor in the re-emergence of Western medicine candidates to treat leukemia and other solid tumors. However, long-term exposure to As has been correlated with numerous disadvantageous influences on health, particularly carcinogenesis. Importantly, accumulating evidence suggests that biotransformation of As, as a step to eliminate As from the human body, can induce alterations at the genetic and epigenetic levels, resulting in therapeutic effects or carcinogenesis. In this article, we aimed to provide a systematic overview of the primary contributions associated with As and its compounds, as well as the detailed mechanisms applied in APL cells and carcinogenic toxicology. This review may help to understand the underlying mechanisms and safe wide clinical applications of medicinal As along with its compounds.

摘要

砷(As)及其各种化合物已经被广泛应用近 4000 年,无论是作为药物还是毒物。这些化合物在治疗从皮肤病到癌症等各种疾病方面具有重要价值,从而强调了它们作为治疗剂的重要作用。砷化合物,特别是三氧化二砷(ATO)在治疗急性早幼粒细胞白血病(APL)方面的能力,从根本上改变了人们对毒物的认识,并成为重新出现的治疗白血病和其他实体瘤的西医候选药物的主要因素。然而,长期接触砷与许多健康方面的不利影响有关,特别是致癌作用。重要的是,越来越多的证据表明,砷的生物转化作为从人体中消除砷的一步,可以诱导遗传和表观遗传水平的改变,从而产生治疗效果或致癌作用。在本文中,我们旨在对砷及其化合物的主要作用及其在 APL 细胞和致癌毒理学中的详细机制进行系统综述。这篇综述可能有助于理解药用砷及其化合物的潜在机制和安全广泛的临床应用。

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