Inhibition of DNA synthesis by phenobarbital in primary cultures of hepatocytes from normal rat liver and from hepatic nodules.
Inhibition of DNA synthesis by phenobarbital in primary cultures of hepatocytes from normal rat liver and from hepatic nodules.
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苯巴比妥对正常大鼠肝脏和肝结节肝细胞原代培养物中 DNA 合成的抑制作用。
DOI：
10.1093/carcin/13.12.2287
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发表时间：
1992
期刊：
影响因子：
4.7
通讯作者：
Sarma,DS
中科院分区：
文献类型：
--
作者：
Manjeshwar,S;Rao,PM;Rajalakshmi,S;Sarma,DS
为解释苯巴比妥 (PB) 促进肝癌发生的机制而提出的众多假设之一是通过对周围肝细胞的差异有丝分裂抑制，同时允许启动的肝细胞对生长刺激做出反应并形成病灶和结节。鉴于 PB 和另一种大鼠肝脏肿瘤促进剂乳清酸 (OA) 之间的结构相似，本研究旨在确定 (i) PB 是否像 OA 一样，在生长因子受体和受体介导的早期事件之外的位点发挥其线粒体抑制作用； (ii) PB是否通过在体外选择性抑制非起始肝细胞而不是起始肝细胞来发挥差异性有丝分裂抑制作用。我们的研究表明，与 OA 一样，PB 也以剂量依赖性方式抑制正常大鼠肝脏肝细胞中的 DNA 合成，在 6 mM 剂量下抑制 80-90%。一个靶位点可能位于生长因子受体介导的早期事件之外，因为 PB 会提前 24 小时抑制用生长因子引发的肝细胞中的 DNA 合成。有趣的是，PB 不仅抑制周围非结节肝脏的肝细胞中的 DNA 合成，而且还抑制由 1,2-二甲基肼起始并用 OA 促进的持续性肝结节的肝细胞中的 DNA 合成。因此，我们的结果表明，尽管 PB 是肝细胞中 DNA 合成的有丝分裂抑制剂，但它似乎不会像耐药肝细胞和 OA 模型中那样在非结节周围肝细胞和起始肝细胞之间产生强烈的差异有丝分裂抑制。这些结果提出了一个问题：差异有丝分裂抑制是否是 PB 介导的大鼠肝脏肿瘤促进的主要影响因素。
One of the many hypotheses put forward to explain the mechanism by which phenobarbital (PB) promotes hepatocarcinogenesis is by differential mitoinhibition of surrounding hepatocytes while allowing the initiated hepatocytes to respond to growth stimuli and form foci and nodules. Given the similarity in structures between PB and orotic acid (OA), another rat liver tumor promoter, the present investigation was designed to determine (i) whether PB, like OA, exerts its mitoinhibitory effect at a site beyond the growth factor receptor and receptor mediated early events; and (ii) whether PB exerts a differential mitoinhibitory effect by selectively inhibiting the non-initiated hepatocytes but not the initiated hepatocytesin vitro. Our studies demonstrate that, like OA, PB also inhibits DNA synthesis in hepatocytes from normal rat liver in a dose dependent manner with 80–90% at a dose of 6 mM. One target site may lie beyond the growth factor receptor mediated early events because PB inhibited DNA synthesis in hepatocytes primed with the growth factor 24 h earlier. Interestingly, PB inhibited DNA synthesis not only in hepatocytes from non-nodular surrounding liver but also in hepatocytes from persistent hepatic nodules initiated with 1,2-dimethylhydra-zine and promoted with OA. Therefore, our results suggest that although PB is a mitoinhibitor of DNA synthesis in hepatocytes, it does not appear to create as strong a differential mitoinhibition between non-nodular surrounding and initiated hepatocyes as is evident in the resistant hepatocyte and OA models. These results raise the question whether differential mitoinhibition is the major contributing factor in the PB mediated rat liver tumor promotion.
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影响因子：
4.4
作者：
G. Gleich;E. Frigas;D. Loegering;D. L. Wassom;D. Steinmuller
通讯作者：
G. Gleich;E. Frigas;D. Loegering;D. L. Wassom;D. Steinmuller
DOI：
--
发表时间：
1980
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
E. Frigas;D. Loegering;G. Gleich
通讯作者：
E. Frigas;D. Loegering;G. Gleich
影响因子：
10
作者：
TURNERWARWICK, M;BURROWS, B;JOHNSON, A
通讯作者：
JOHNSON, A
人类嗜酸性粒细胞氧化代谢酶 1
DOI：
--
发表时间：
1978
期刊：
Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
影响因子：
--
作者：
L. Dechatelet;R. Migler;P. Shirley;D. Bass;C. McCall
通讯作者：
C. McCall
间质性肺疾病患者肺实质中炎症和免疫效应细胞的特征。
DOI：
--
发表时间：
2015
期刊：
American Review of Respiratory Disease
影响因子：
--
作者：
G. Hunninghake;O. Kawanami;V. Ferrans;R. Young;W. Roberts;R. Crystal
通讯作者：
R. Crystal