Mutagen activation of 1,2-dibromo-3-chloropropane by cytosolic glutathione S-transferases and microsomal enzymes.
Mutagen activation of 1,2-dibromo-3-chloropropane by cytosolic glutathione S-transferases and microsomal enzymes.
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胞质谷胱甘肽 S-转移酶和微粒体酶对 1,2-二溴-3-氯丙烷的诱变激活。
DOI：
10.1080/15287398609530948
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Kulkarni,AP
中科院分区：
文献类型：
--
作者：
Miller,GE;Brabec,MJ;Kulkarni,AP
目前尚不清楚谷胱甘肽（CSH）与1,2‐二溴‐3‐氯丙烷（DBCP）偶联是否会导致基因毒性激活。因此，在改良的Ames系统中，我们评估了未诱导大鼠肝脏的S9、细胞质和微粒体组分激活DBCP的相对能力。S9酶单独或与外源CSH联合作用均不增强DBCP的致突变性；用胞质酶得到了相同的结果。在NADPH存在的情况下，S9或微粒体部分都能产生显著的DBCP诱变激活。激活与细胞色素P - 450浓度成正比，并被外源性GSH减弱。CSH对遗传毒性的保护不需要胞质谷胱甘肽S转移酶（GST）。因此，用S9组分获得的DBCP的诱变激活主要是由于微粒体而不是细胞质酶的生物转化。细胞质溶胶催化CSH与DBCP结合的动力学研究揭示了表观kmax和Vmax的组织特异性差异。与肝脏CSTs（31.2±7.9 nmol/min•mg蛋白）相比，肾脏和睾丸CSTs的vmax值降低了28-46%。然而，肾脏和睾丸gst对DBCP的亲和力相对较高。因此，肝外组织具有将CSH与DBCP结合的显著能力。DBCP - CSH缀合物可能经过肝外肽酶和β裂解酶的酶修饰，产生其他可能介导DBCP肝外毒性的含硫部分。
It is not clear whether glutathione (CSH) conjugation to 1,2‐dibromo‐3‐chloropro‐pane (DBCP) results in genotoxic activation. Therefore S9, cytosolic, and microsomal fractions from uninduced rat liver were evaluated for their relative ability to activate DBCP in a modified Ames system. The S9 enzymes, either alone or in combination with exogenous CSH, did not enhance the mutagenicity of DBCP; identical results were obtained with cytosolic enzymes. Significant mutagenic activation of DBCP was produced by either S9 or microsomal fractions in the presence of NADPH. Activation was proportional to cytochrome P‐450 concentrations, and was diminished by exogenous GSH. The protection against genotoxicity exerted by CSH did not require cytosolic glutathione S‐transferases (GST). Thus, mutagenic activation of DBCP as obtained with S9 fractions is primarily due to biotransformation by microsomal rather than by cytosolic enzymes. Kinetic studies of cytosol‐catalyzed conjugation of CSH to DBCP revealed tissue‐specific differences in apparent Kmand Vmax. Renal and tes‐ticular CSTs were associated with 28–46% smaller Vmaxvalues when compared to hepatic CSTs (31.2 ± 7.9 nmol/min • mg protein). However, renal and testicular GSTs had relatively higher affinities for DBCP. Thus, extrahepatic tissues possess significant capacity to conjugate CSH to DBCP. DBCP‐CSH conjugates may undergo enzymatic modification by extrahepatic peptidases and β‐lyase to yield other sulfur‐containing moieties that perhaps mediate DBCP's extrahepatic toxicity.
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影响因子：
3.6
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
J. Hook
DBCP 代谢物大分子结合与坏死致病性的相关性：大鼠 DBCP 的代谢命运（第 3 部分）
DOI：
--
发表时间：
1980
期刊：
影响因子：
--
作者：
Y. Kato;Kiyoshi Sato;T. Harada;S. Maki;O. Matano;S. Goto
通讯作者：
S. Goto
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DOI：
--
发表时间：
1980
期刊：
Mutation research
影响因子：
--
作者：
J. Rosen;Y. Segall;J. Casida
通讯作者：
J. Casida