Hesse S, Jernström B, Martinez M, Moldéus P, Christodoulides L, Ketterer B
Carcinogenesis. 1982;3(7):757-61. doi: 10.1093/carcin/3.7.757.
The binding to DNA of reactive metabolites of trans-7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (BP-7,8-diol) was studied following the incubation of tritiated benzo[a]pyrene (BP) and BP-7,8-diol with nuclei from livers of 3-methylcholanthrene-treated rats. Binding was inhibited to a small extent by glutathione (GSH) alone and to a much greater extent by GSH and cytosol or purified GSH-transferases B and E. In this respect GSH-transferases A and C were also active, but less so. Inhibition of binding of BP-7,8-diol metabolites to DNA mediated by GSH-transferases was associated with the formation of GSH conjugates. The extent of inhibition of binding was similar in incubations of nuclei alone, nuclei and rat liver microsomes, and calf thymus DNA and rat liver microsomes. This indicates that reactive metabolites of BP-7,8-diol, formed either by nuclei or microsomes, are readily accessible to soluble GSH-transferases. GSH and cytosol were also active in inhibiting DNA-binding of reactive metabolites from 9-hydroxybenzo[a]pyrene (9-OH-BP). Thus, in the rat hepatocyte GSH and GSH-transferases may be important in protecting DNA from electrophilic attack by reactive BP-7,8-diol and 9-OH-BP species.
在将氚标记的苯并[a]芘（BP）和反式-7,8-二氢-7,8-二羟基苯并[a]芘（BP-7,8-二醇）与经3-甲基胆蒽处理的大鼠肝脏细胞核一起温育后，研究了BP-7,8-二醇的反应性代谢产物与DNA的结合情况。单独的谷胱甘肽（GSH）对结合有轻微抑制作用，而GSH与胞液或纯化的谷胱甘肽转移酶B和E一起时对结合的抑制作用则大得多。在这方面，谷胱甘肽转移酶A和C也有活性，但活性较低。谷胱甘肽转移酶介导的BP-7,8-二醇代谢产物与DNA结合的抑制作用与谷胱甘肽共轭物的形成有关。在单独细胞核的温育、细胞核与大鼠肝脏微粒体的温育以及小牛胸腺DNA与大鼠肝脏微粒体的温育中，结合抑制的程度相似。这表明，由细胞核或微粒体形成的BP-7,8-二醇的反应性代谢产物很容易被可溶性谷胱甘肽转移酶作用。GSH和胞液在抑制9-羟基苯并[a]芘（9-OH-BP）的反应性代谢产物与DNA结合方面也有活性。因此，在大鼠肝细胞中，GSH和谷胱甘肽转移酶在保护DNA免受反应性BP-7,8-二醇和9-OH-BP物种的亲电攻击方面可能很重要。
