Studies on the in vitro transfer of DNA binding benzo[a]pyrene metabolites from rat hepatocytes to human fibroblasts.
Studies on the in vitro transfer of DNA binding benzo[a]pyrene metabolites from rat hepatocytes to human fibroblasts.
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DNA结合苯并[a]芘代谢物从大鼠肝细胞体外转移至人成纤维细胞的研究。
DOI：
10.1093/carcin/2.11.1151
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发表时间：
1981
期刊：
影响因子：
4.7
通讯作者：
Söderhäll,S
中科院分区：
文献类型：
--
作者：
Nordenskjöld,M;Svensson,SA;Jernström,B;Moldéus,P;Dock,L;Söderhäll,S
研究了苯并[a]吡喃(BP)代谢产物在体外孵育的大鼠肝细胞中的释放和重吸收。肝细胞快速摄取BP，随后排出有机和水溶性代谢物。在进一步培养时，BP-二氢二酚和BP-苯酚被细胞重新吸收，最终以水溶性结合物的形式排出。肝细胞对BP的代谢也导致活性中间体的形成和释放到孵育液中。细胞释放出稳定的withtrans-7，8-dihydroxy-7，8-dihydrobenzo-[a]pyrene和9-羟基苯并-4，5-氧化物(S)。BP代谢物可与肝细胞和成纤维细胞DNA结合。DNA结合的程度通过DNA链断裂的形成来估计。BP代谢产物在肝细胞内形成，并转移到成纤维细胞，在成纤维细胞中诱导DNA链断裂。在培养液中加入DNA可显著降低这些细胞中单链DNA的比例。在肝细胞排泄BP-苯酚和BP二氢二酚增加的条件下，成纤维细胞的DNA链断裂数量增加。
The release and reabsorption of benzo[a]pyreme (BP) metabolites were studied in isolated rat hepatocytes in cubated with BP. There was a rapid uptake of BP by the hepatocytes which was followed by an excretion of organic as well as water-soluble metabolltes. Upon further incubation the BP-dihydrodiols and BP-phenols were reabsorbed by the cells and finally excreted as water-soluble conjugates. The metabolism of BP by the hepatocytes aLso resulted in the formation and release of reactive intermediates to the incubation medium. The DNA-binding intermediates released from the cells were consistent withtrans-7,8-dihydroxy-7,8-dihydrobenzo-[a]pyrene and 9-hydroxybenzo 4,5-oxide(s). The BP-metabolites were found to bind to hepatocyte and fibroblast DNA. The degree of DNA binding was estimated as the formation of DNA strand breaks. BP metabolites formed within the hepatocytes and transferred to the fibroblasts were found to induce DNA strand breaks in the latter cells. Addition of DNA to the medium markedly decreased the fraction of single stranded DNA in these cells. Under conditions where the excretion from hepatocytes of BP-phenols and BP dihydrodiols were increased, the amount of DNA strand breaks in the fibroblasts increased.