The covalent binding of acetaminophen to cellular nucleic acids as the result of the respiratory burst of neutrophils derived from the HL-60 cell line.
The covalent binding of acetaminophen to cellular nucleic acids as the result of the respiratory burst of neutrophils derived from the HL-60 cell line.
复制标题
由于 HL-60 细胞系中性粒细胞呼吸爆发，对乙酰氨基酚与细胞核酸共价结合。
DOI：
10.1016/0041-008x(92)90011-g
复制
发表时间：
1992
影响因子：
3.8
通讯作者：
Quintana,SJ
中科院分区：
文献类型：
--
作者：
Corbett,MD;Corbett,BR;Hannothiaux,MH;Quintana,SJ
白血病细胞系HL-60的培养物在被诱导分化为嗜酸性类型后，能够在刺激呼吸爆发时引起对乙酰氨基酚的生物活化和核酸结合。发现这种现象模拟了与先前用正常人粒细胞显示的相同的过程。通过使用14 C标记的对乙酰氨基酚同类物定量测定与细胞DNA和RNA的结合。蛋白质结合的程度与RNA结合的程度大致相同。用[环-14 C]-和[14 C-O]对乙酰氨基酚同时进行的标记实验进一步表明，对乙酰氨基酚分子以完整的方式与DNA结合，而与RNA的结合显示出对乙酰氨基酚环相对于羰基约50%的过量结合。某些抑制剂的实验表明，过氧化氢酶和叠氮离子强烈抑制DNA结合，而超氧化物歧化酶对结合有轻微的刺激作用。这些结果表明髓过氧化物酶在生物活化过程中的重要作用，这与某些芳胺化合物的生物活化机制形成对比。对乙酰氨基酚与核酸结合的机制是需要底物1 e−氧化为苯氧基自由基，尽管N-乙酰基-对-苯醌亚胺代谢物的产生也可能有助于这种结合，而N-乙酰基-对-苯醌亚胺代谢物被认为是对乙酰氨基酚与蛋白质结合的原因。考虑到对乙酰氨基酚可能是一种独特的途径，可将该化学品代谢为核酸结合物质，因此考虑了对乙酰氨基酚的潜在遗传毒性。
After being induced to differentiate into a neutrophilic type, cultures of the leukemic cell line HL-60 were able to cause the bioactivation and nucleic acid binding of acetaminophen upon stimulation of the respiratory burst. This phenomenon was found to simulate the same process as that previously shown with normal human granulocytes. Binding to both DNA and RNA of the cells was determined quantitatively by use of14C-labeled acetaminophen congeners. Protein binding occurred to about the same extent as did RNA binding. Simultaneous labeling experiments with [ring-14C]-and [14CO]acetaminophen further showed that the acetaminophen molecule was bound to DNA in an intact manner, while binding to RNA showed about a 50% excess binding of the acetaminophen ring relative to the carbonyl group. Experiments with certain inhibitors showed that catalase and azide ion strongly inhibited DNA binding, while superoxide dismutase had a slight stimulatory effect on binding. These results suggest a significant role for myeloperoxidase in the bioactivation process, which contrasts with the proposed bioactivation mechanism of certain arylamine compounds. A mechanism was proposed for acetaminophen binding to nucleic acids that requires the 1 e−oxidation of this substrate to its phenoxyl radical, although the production of the N-acetyl-p-benzoquinoneimine metabolite, which has been proposed to account for the extensive protein binding known to occur for acetaminophen, might also contribute to such binding. The potential genotoxicity of acetaminophen was considered in view of what might be a unique pathway which can metabolize this chemical to a nucleic acid-binding species.
登录
查看更多内容
DOI：
10.1073/pnas.75.5.2458
发表时间：
1978-01-01
影响因子：
11.1
作者：
COLLINS, SJ;RUSCETTI, FW;GALLO, RC
通讯作者：
GALLO, RC
测量人类中性粒细胞产生的 O2-。
影响因子：
--
作者：
M. Markert;P. Andrews;B. Babior
通讯作者：
B. Babior
5,5-Dimethyloxazolidine-2,4-dione 是人类早幼粒细胞白血病 (HL-60) 细胞分化的强诱导剂。
DOI：
10.1016/0922-3371(89)90749-1
发表时间：
1989
期刊：
Cell differentiation and development : the official journal of the International Society of Developmental Biologists
影响因子：
--
作者：
Calderon,TM;Schneiderman,N;Michl,J;Christman,JK
通讯作者：
Christman,JK
人粒细胞呼吸爆发对乙酰氨基酚和相关芳胺底物的代谢激活和核酸结合。
影响因子：
4.1
作者：
Corbett,MD;Corbett,BR;Hannothiaux,MH;Quintana,SJ
通讯作者：
Quintana,SJ
HL-60 细胞系和人粒细胞对芳基胺和相关异生物质生物活性影响的比较。
影响因子：
5.1
作者：
Corbett,MD;Hannothiaux,MH;Corbett,BR;Quintana,SJ
通讯作者：
Quintana,SJ