Carcinogen induced asynchronous replication of polyoma DNA is mediated by a trans-acting factor.
Carcinogen induced asynchronous replication of polyoma DNA is mediated by a trans-acting factor.
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致癌物诱导的多瘤 DNA 异步复制是由反式作用因子介导的。
DOI：
10.1093/carcin/7.6.1011
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发表时间：
1986
期刊：
影响因子：
4.7
通讯作者：
Weinstein,IB
中科院分区：
文献类型：
--
作者：
Lambert,ME;Pellegrini,S;Gattoni-Celli,S;Weinstein,IB
我们已经证明，致癌物质对 DNA 的损伤会诱导细胞因子的产生，这些细胞因子反过来增强多瘤病毒 DNA 的异步复制。将多瘤病毒转化的大鼠细胞系暴露于苯并[a]芘-7, 8-二醇-9, 10-氧化物（BPDE）（苯并[a]芘的最终致癌代谢物），导致大小不一的游离病毒DNA分子的积累，其中含有多瘤起源序列以及整合病毒DNA侧翼的细胞序列。当序列gpt与多瘤早期区域连接并转染到大鼠细胞中时，它会经历异步复制，以响应用BPDE直接处理转染细胞，或响应未处理的转染细胞与先前暴露于BPDE的正常细胞的融合。与 BPDE 相比，羟基脲、异亮氨酸剥夺或甲氨蝶呤对细胞周期的短暂停滞导致病毒 DNA 复制略有增强。阿菲迪霉素（DNA 聚合酶 α 的抑制剂）和 3-氨基苯甲酰胺（聚[ADP]核糖基转移酶的抑制剂）均能显着抑制 BPDE 诱导的病毒 DNA 合成。响应细胞DNA损伤而诱导α反式作用因子可能与细胞转化中环境化学物质和DNA病毒之间的协同相互作用以及基因扩增的一般现象有关。
We have demonstrated that carcinogen damage to DNA induces the production of cellular factors that act intransto enhance the asynchronous replication of polyoma viral DNA. Exposure of a polyoma virus-transformed rat cell line to benzo[a]pyrene-7, 8-diol-9, 10-oxide (BPDE), the ultimate carcinogenic metabolite of benzo[a]pyrene, led to the accumulation of heterogeneously sized free viral DNA molecules which contain polyoma origin sequences as well as cellular sequences that flank the integrated viral DNA. When the sequencegptwas linked to the polyoma early region and transfected into rat cells, it underwent asynchronous replication in response either to direct treatment of the transfected cells with BPDE, or to fusion of untreated transfected cells with normal cells previously exposed to BPDE. Transient arrest of the cell cycle by hydroxyurea, isoleucine deprivation or methotrexate caused a slight enhancement of viral DNA replication when compared with BPDE. Both aphidicolin, an inhibitor of DNA polymerase alpha, and 3-aminobenzamide, an inhibitor of poly[ADP]ribosyI transferase, caused marked inhibition of BPDE-induced viral DNA synthesis. The induction of atrans-acting factor in response to damage of cellular DNA may be relevant to synergistic interactions between environmental chemicals and DNA viruses in cell transformation and to the general phenomenon of gene amplification.