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新陈代谢与砷的矛盾效应:致癌与抗癌

Metabolism and the paradoxical effects of arsenic: carcinogenesis and anticancer.

作者信息

Cui Xing, Kobayashi Yayoi, Akashi Makoto, Okayasu Ryuichi

机构信息

Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Chiba 263-8555, Japan.

出版信息

Curr Med Chem. 2008;15(22):2293-304. doi: 10.2174/092986708785747526.

Abstract

Arsenic, a known human carcinogen, can induce tumors of the skin, urinary bladder, liver and lung etc.. On the other hand, arsenic is also a novel promising anticancer agent, and can be used effectively to treat acute promyelocytic leukemia (APL) and some other tumors. These paradoxical effects of arsenic not only result from direct or indirect influences on the genetic and epigenetic levels, but are also closely correlated with unique arsenic metabolism. This article reviews our recent studies as well as other reports on arsenic metabolism and epigenetic changes of DNA methylation during its metabolism. We also summarize the clinical use of arsenic trioxide (As2O3) to date and discuss new therapeutic strategies such as concurrent arsenic-radiation therapy to achieve local tumor control and enhance the radiosensitivity of solid tumors.

摘要

砷是一种已知的人类致癌物,可诱发皮肤、膀胱、肝脏和肺部等部位的肿瘤。另一方面,砷也是一种有前景的新型抗癌剂,可有效用于治疗急性早幼粒细胞白血病(APL)和其他一些肿瘤。砷的这些矛盾作用不仅源于对基因和表观遗传水平的直接或间接影响,还与独特的砷代谢密切相关。本文综述了我们最近的研究以及其他关于砷代谢及其代谢过程中DNA甲基化表观遗传变化的报道。我们还总结了迄今为止三氧化二砷(As2O3)的临床应用,并讨论了新的治疗策略,如联合砷-放射治疗以实现局部肿瘤控制并提高实体瘤的放射敏感性。

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