THE ROLE OF THE METHYLATION IN THE DETOXICATION OF ARSENATE IN THE RABBIT
THE ROLE OF THE METHYLATION IN THE DETOXICATION OF ARSENATE IN THE RABBIT
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DOI：
10.1016/0009-2797(85)90008-0
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发表时间：
1985-12-01
影响因子：
5.1
通讯作者：
ENVALL, J
中科院分区：
文献类型：
--
作者：
MARAFANTE, E;VAHTER, M;ENVALL, J
本文研究了砷在兔体内的生物转化、组织滞留、细胞内结合和生物动力学。注射高碘酸氧化腺苷(PAD)抑制甲基转移酶的活性，使[74As]二甲基丙氨酸(DMA)的生成显著减少，从而使组织中74As的水平增加1.5-4倍。这几乎与报道的服用亚砷酸盐和PAD的兔子相同，这是由于结合到组织上的砷酸盐迅速还原为亚砷酸盐。只有大约30%的砷酸盐在尿液中没有变化地排出，这表明很大一部分被还原为AsIII。因此，DNA的甲基化对于砷酸盐暴露后的解毒作用似乎与亚砷酸盐暴露后的解毒作用几乎一样重要。在甲基化能力正常的兔中，50-70%的AsIII产物甲基化为DMA。肝脏是给药后1小时内唯一存在DNA的器官，表明这是甲基化的主要部位。除甲状腺外，所有组织中的DNA都被迅速清除。
The biotransformation, tissue retention, intracellular binding and biokinetics of arsenic were studied in rabbits exposed to [74As]arsenate (0.4 mg As/kg body wt., i.v.). Inhibition of the methyltransferase activity by injection of periodate-oxidized adenosine (PAD) caused a marked decrease of the formation of [74As]dimethylarsinic acid (DMA), which gave rise to 1.5-4 times increased tissue levels of 74As. This is almost the same as reported for rabbits given arsenite in combination with PAD and was due to a rapid reduction of the arsenate to arsenite which bound to the tissues. Only about 30% of the arsenate given was excreted unchanged in the urine, indicating that a large part was reduced to AsIII. Thus the methylation to DMA seems to be almost as important for the detoxication following exposure to arsenate as that following exposure to arsenite. In the rabbits with normal methylating capacity 50-70% of the produced AsIII was methylated to DMA. The liver was the only organ in which DNA was present 1 h after the administration, indicating that this is the main site of the methylation. The DMA was rapidly cleared from all tissues except the thyroid.