Modulation of microsome-mediated aflatoxin B1 binding to exogenous and endogenous DNA by cytosolic glutathione S-transferases in rat and hamster livers.
Modulation of microsome-mediated aflatoxin B1 binding to exogenous and endogenous DNA by cytosolic glutathione S-transferases in rat and hamster livers.
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大鼠和仓鼠肝脏中胞质谷胱甘肽 S-转移酶调节微粒体介导的黄曲霉毒素 B1 与外源和内源 DNA 的结合。
DOI：
10.1093/carcin/5.2.269
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发表时间：
1984
期刊：
影响因子：
4.7
通讯作者：
Clearfield,MS
中科院分区：
文献类型：
--
作者：
Lotlikar,PD;Jhee,EC;Insetta,SM;Clearfield,MS
在大鼠和仓鼠肝脏中研究了微粒体介导的黄曲霉毒素B_1（AFB_1）与外源和内源DNA的结合及其受细胞内谷胱甘肽（GSH）S-转移酶的调节。在较宽的胞液浓度范围内进行的动力学研究表明，仓鼠胞液抑制黄曲霉毒素B1与外源性小牛胸腺DNA结合的有效性比大鼠胞液高几倍。低浓度的GSH（0.1-0.2 mM）需要50%的抑制AFB 1-DNA结合的细胞质。与外源性DNA，结合微粒体细胞质组分从仓鼠给更多的AFB 1-DNA结合比那些从大鼠。然而，细胞核作为内源性DNA的来源，黄曲霉毒素B1-DNA结合是从仓鼠的微粒体-细胞质组分比从大鼠。在1 mM的三氯环氧丙烷或氧化苯乙烯存在下，AFB 1-DNA结合的胞质抑制几乎完全逆转。AFB_1-DNA结合和AFB_1-GSH结合的定量表明这两个过程之间呈反比关系。大鼠胞浆形成AFB 1-GSH结合物的能力低于仓鼠。两个物种的肝脏GSH水平大致相等（6-7 mM）。处死前12 h腹腔注射[14 C] AFB 1，大鼠的AFB 1与肝细胞核DNA的结合率高于仓鼠。然而，腹腔注射马来酸二乙酯（600 mg/kg）使肝脏GSH水平降低80%，使两种物种的AFB 1-DNA结合增加2至3倍。本文还讨论了大鼠和仓鼠细胞内谷胱甘肽S-转移酶在调节肝黄曲霉毒素B1-DNA结合中的作用。
Microsome mediated aflatoxin B1(AFB1) binding to exogenous and endogenous DNA and its modulation by cytosolic glutathione (GSH) S-transferases have been examined in rat and hamster livers. Kinetic studies over a wide range of cytosol concentrations indicate that cytosol from the hamster is several-fold more effective than that from the rat in inhibiting AFB1binding to exogenous calf thymus DNA mediated by microsomes from either species. Low concentrations of GSH (0.1–0.2 mM) are required for 50% inhibition of AFB1—DNA binding by cytosol. With exogenous DNA, combined microsome-cytosol fractions from the hamster give more AFB1—DNA binding than those from the rat. However, with nuclei as a source of endogenous DNA, AFB1—DNA binding is less with combined microsome-cytosol fractions from the hamster than those from the rat. Cytosolic inhibition of AFB1—DNA binding is almost completely reversed in the presence of 1 mM levels of either trichloropropene oxide or styrene oxide. Quantitation of AFB1—DNA binding and AFB1-GSH conjugation indicate an inverse relationship between these two processes. Cytosol from the rat has less capacity than that from the hamster to form an AFB1—GSH conjugate. Hepatic GSH levels are about equal (6–7 mM) in both species. I.p. administration of [14C]AFB12 h before sacrifice gives more AFB1binding to hepatic nuclear DNA in rats than in hamsters. However, depletion of hepatic GSH levels by 80% by i.p. administration of diethylmaleate (600 mg/kg) increases AFB1—DNA binding 2- to 3-fold in both species. The role of cytosolic GSH S-transferases in modulating hepatic AFB1—DNA binding in rats and hamsters is discussed.