Arsenic trioxide
描述
Arsenic trioxide is a chemotheraputic agent of idiopathic function used to treat leukemia that is unresponsive to first line agents. It is suspected that arsenic trisulfide induces cancer cells to undergo apoptosis. Due to the toxic nature of arsenic, this drug carries significant health risks. The enzyme thioredoxin reductase has recently been identified as a target for arsenic trioxide.
类别
"Drug", "Pesticide", "Pollutant", "Airborne Pollutant", "Synthetic Toxin"
同义词
"Areseneous oxide", "Arseneous anhydride", "Arsenic sesquioxide", "Arsenic(III) oxide", "Arsenious acid", "Arsenious Trioxide", "Arsentrioxide", "Diarsenic trioxide", "White arsenic"
IUPAC 名称
bicyclo[1.1.1]diarsoxane
简化分子线性输入规范
O1[As]2O[As]1O2
InChI 标识符
InChI=1S/As2O3/c3-1-4-2(3)5-1
键
InChIKey=GOLCXWYRSKYTSP-UHFFFAOYSA-N
化合物类型
Inorganic compounds
大分类
Mixed metal/non-metal compounds
类型
Miscellaneous mixed metal/non-metals
子类
Miscellaneous metallic oxoanionic compounds
直接大类
Miscellaneous arsenites
另外分类
"Inorganic salts", "Metalloid salts", "Trivalent inorganic arsenic compounds"
取代基
"Arsenite", "Inorganic arsenic compound", "Inorganic metalloid salt", "Inorganic salt", "Trivalent inorganic arsenic compound"
地位
Detected and Not Quantified
蜂窝位置
"Cytoplasm", "Membrane"
熔点/沸点/溶解度
465°C//1.7E+004 mg/L (at 16°C)
暴露途径
Oral (L2) ; inhalation (L2) ; dermal (L2)
毒性机制
The mechanism of action of Arsenic Trioxide is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein PML/RAR-alpha. It is suspected that arsenic trioxide induces cancer cells to undergo apoptosis. Arsenic and its metabolites disrupt ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. Arsenic's carginogenicity is influenced by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. The binding of other arsenic protein targets may also cause altered DNA repair enzyme activity, altered DNA methylation patterns and cell proliferation. (T1, A17)
代谢
Arsenic is mainly absorbed by inhalation or ingestion, and to a lesser extent by dermal exposure. It is then distributed throughout the body, where it is reduced into arsenite if necessary, then methylated into monomethylarsenic (MMA) and dimethylarsenic acid (DMA) by arsenite methyltransferase. Arsenic and its metabolites are primarily excreted in the urine. Arsenic is known to induce the metal-binding protein metallothionein, which decreases the toxic effects of arsenic and other metals by binding them and making them biologically inactive, as well as acting as an antioxidant. (L20) The metabolism of arsenic trioxide involves reduction of pentavalent arsenic to trivalent arsenic by arsenate reductase and methylation of trivalent arsenic to monomethylarsonic acid and monomethylarsonic acid to dimethylarsinic acid by methyltransferases. The main site of methylation reactions appears to be the liver. Arsenic is stored mainly in liver, kidney, heart, lung, hair and nails.Route of Elimination: Trivalent arsenic is mostly methylated in humans and excreted in urine.
毒性值
LD50: 871 mg/kg (Intraperitoneal, Rat) (T14)
LD50: 31 500 ug/kg (Oral, Mouse) (T14)
LD50: 9800 ug/kg (Subcutaneous, Mouse) (T14)
LD50: 10 700 ug/kg (Intravenous, Mouse) (T14)
致死剂量
200 mg for an adult human. (T17)
致癌性
1, carcinogenic to humans. (L135)
用途/来源
Arsenic trioxide is a byproduct of certain kinds of ore processing. It is the starting point for the manufacture of many arsenic-based products, including pesticides, pharamaceuticals, alloys, and semiconductors. It is also used as a wood preservative and decolorizing agent. (L718) It is also use for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL), and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
最低风险等级
Acute Oral: 0.005 mg/kg/day (L134)
Chronic Oral: 0.0003 mg/kg/day (L134)
Chronic Inhalation: 0.01 mg/m3 (L134)
健康影响
Arsenic poisoning can lead to death from multi-system organ failure, probably from necrotic cell death, not apoptosis. Arsenic is also a known carcinogen, especially in skin, liver, bladder and lung cancers. (T1, L20)
症状
Symptoms of overdose include convulsions, muscle weakness and confusion. Exposure to lower levels of arsenic can cause nausea and vomiting, decreased production of red and white blood cells, abnormal heart rhythm, and damage to blood vessels.
治疗
Arsenic poisoning can be treated by chelation therapy, using chelating agents such as dimercaprol, EDTA or DMSA. Charcoal tablets may also be used for less severe cases. In addition, maintaining a diet high in sulfur helps eliminate arsenic from the body. (L20)
创建于
2009-03-06 18:58:19 UTC
更新于
2014-12-24 20:21:22 UTC
目标
| 毒素T3DB ID | 毒素名称 | 目标名称 |
|---|
| T3D0224 |
Arsenic trioxide |
Tubulin beta-8 chain-like protein LOC260334 |
| T3D0224 |
Arsenic trioxide |
Tubulin beta-8 chain |
| T3D0224 |
Arsenic trioxide |
Tubulin beta-6 chain |
| T3D0224 |
Arsenic trioxide |
Tubulin beta-4A chain |
| T3D0224 |
Arsenic trioxide |
Tubulin beta-3 chain |
| T3D0224 |
Arsenic trioxide |
Tubulin beta-4B chain |
| T3D0224 |
Arsenic trioxide |
Tubulin beta-2B chain |
| T3D0224 |
Arsenic trioxide |
Tubulin beta-2A chain |
| T3D0224 |
Arsenic trioxide |
Tubulin beta-1 chain |
| T3D0224 |
Arsenic trioxide |
Tubulin alpha-8 chain |
| T3D0224 |
Arsenic trioxide |
Tubulin alpha-4A chain |
| T3D0224 |
Arsenic trioxide |
Tubulin alpha-3E chain |
| T3D0224 |
Arsenic trioxide |
Tubulin alpha-3C/D chain |
| T3D0224 |
Arsenic trioxide |
Tubulin alpha-1C chain |
| T3D0224 |
Arsenic trioxide |
Tubulin alpha-1B chain |
| T3D0224 |
Arsenic trioxide |
Tubulin alpha-1A chain |
| T3D0224 |
Arsenic trioxide |
Tubulin alpha chain-like 3 |
| T3D0224 |
Arsenic trioxide |
Pyruvate dehydrogenase protein X component, mitochondrial |
| T3D0224 |
Arsenic trioxide |
Putative tubulin-like protein alpha-4B |
| T3D0224 |
Arsenic trioxide |
Putative tubulin beta-4q chain |
| T3D0224 |
Arsenic trioxide |
Putative tubulin beta chain-like protein ENSP00000290377 |
| T3D0224 |
Arsenic trioxide |
RAC-alpha serine/threonine-protein kinase |
| T3D0224 |
Arsenic trioxide |
Mitogen-activated protein kinase 1 |
| T3D0224 |
Arsenic trioxide |
Mitogen-activated protein kinase 3 |
| T3D0224 |
Arsenic trioxide |
G1/S-specific cyclin-D1 |
| T3D0224 |
Arsenic trioxide |
Transcription factor AP-1 |
| T3D0224 |
Arsenic trioxide |
Inhibitor of nuclear factor kappa-B kinase subunit beta |
| T3D0224 |
Arsenic trioxide |
Protein PML |
| T3D0224 |
Arsenic trioxide |
Thioredoxin reductase 3 |
| T3D0224 |
Arsenic trioxide |
Thioredoxin reductase 2, mitochondrial |
| T3D0224 |
Arsenic trioxide |
Thioredoxin reductase 1, cytoplasmic |
| T3D0224 |
Arsenic trioxide |
Actin, cytoplasmic 2 |
| T3D0224 |
Arsenic trioxide |
Actin, cytoplasmic 1 |
| T3D0224 |
Arsenic trioxide |
Tubulin beta chain |
| T3D0224 |
Arsenic trioxide |
Poly [ADP-ribose] polymerase 1 |
| T3D0224 |
Arsenic trioxide |
Kelch-like ECH-associated protein 1 |
| T3D0224 |
Arsenic trioxide |
Glutathione reductase, mitochondrial |
| T3D0224 |
Arsenic trioxide |
Glucocorticoid receptor |
| T3D0224 |
Arsenic trioxide |
Estrogen receptor alpha |
| T3D0224 |
Arsenic trioxide |
Haptoglobin |
| T3D0224 |
Arsenic trioxide |
Hemoglobin subunit alpha |
| T3D0224 |
Arsenic trioxide |
Hemoglobin subunit beta |
| T3D0224 |
Arsenic trioxide |
Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial |
| T3D0224 |
Arsenic trioxide |
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial |
| T3D0224 |
Arsenic trioxide |
Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial |
| T3D0224 |
Arsenic trioxide |
DNA repair protein complementing XP-A cells |
| T3D0224 |
Arsenic trioxide |
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial |
| T3D0224 |
Arsenic trioxide |
Actin, gamma-enteric smooth muscle |
| T3D0224 |
Arsenic trioxide |
Actin, aortic smooth muscle |
| T3D0224 |
Arsenic trioxide |
Actin, alpha skeletal muscle |
| T3D0224 |
Arsenic trioxide |
Actin, alpha cardiac muscle 1 |