Inhibition of RNA synthesis by benzene metabolites and their covalent binding to DNA in rabbit bone marrow mitochondria in vitro.
Inhibition of RNA synthesis by benzene metabolites and their covalent binding to DNA in rabbit bone marrow mitochondria in vitro.
复制标题
苯代谢物对 RNA 合成的抑制及其体外与兔骨髓线粒体 DNA 的共价结合。
DOI：
10.1002/ajim.4700070512
复制
发表时间：
1985
影响因子：
3.5
通讯作者：
Rushmore,TH
中科院分区：
文献类型：
--
作者：
Kalf,GF;Snyder,R;Rushmore,TH
在体外与苯代谢物孵育的兔骨髓细胞的线粒体显示出线粒体RNA合成的浓度依赖性抑制。每种代谢产物的50%摩尔抑制浓度测定为对苯醌，2 × 10−6;苯酚，2.5 × 10−5;对苯二酚，5 × 10 −5;邻苯二酚，2 × 10−3;苯，1.6 × 10−2。体外放射性标记苯与线粒体DNA共价结合的活化代谢物。标记的脱氧核苷是从用[3 H]dGTP预标记DNA并在体外暴露于[14 C]苯的有丝分裂体中分离的DNA酶促产生的，在Sephadex LH-20柱上进行色谱分析，以获得脱氧核苷加合物。洗脱图谱表明mtDNA含有7个脱氧鸟苷加合物。在一个类似的实验中，用[3 H]dATP预标记mtDNA，表明在体外苯可以形成两个mtDNA的脱氧腺苷加合物。对几种脱氧鸟苷加合物的初步鉴定表明，由苯产生的对苯醌、对苯二酚、苯酚和1，2，4-苯三醇与鸟嘌呤形成加合物。
Mitoplasts from rabbit bone marrow cells in vitro incubated with benzene metabolites showed a concentration‐dependent inhibition of mitochondrial RNA synthesis. The 50% molar inhibitory concentration for each metabolite was determined to be p‐benzoquinone, 2 × 10−6; phenol, 2.5 × 10−5; hydroquinone, 5 × 10−5; catechol, 2 × 10−3; benzene, 1.6 × 10−2. Activated metabolites of radiolabeled benzene covalently bound to mitochondrial DNA in vitro. Labeled deoxynucleosides, enzymatically produced from DNA isolated from mitoplasts prelabeled in DNA with [3H]dGTP and exposed to [14C]benzene in vitro, were chromatographed on a Sephadex LH‐20 column to obtain deoxynucleoside‐adducts. The elution profiles indicated that mtDNA contained seven deoxyguanosine‐adducts. A similar experiment in which the mtDNA was prelabeled with [3H]dATP indicated that two deoxyadenosine‐adducts of mt DNA were formed from benzene in vitro. Tentative identification of several deoxyguanosine‐adducts indicates that p‐benzoquinone, hydroquinone, phenol, and 1,2,4‐benzenetriol produced from benzene form adducts with guanine.