Inhibition of macromolecular binding of benzo(a)pyrene and inhibition of neoplasia by disulfiram in the mouse forestomach.
Inhibition of macromolecular binding of benzo(a)pyrene and inhibition of neoplasia by disulfiram in the mouse forestomach.
复制标题
双硫仑抑制小鼠前胃中苯并（a）芘的大分子结合和抑制肿瘤形成。
DOI：
10.1093/jnci/57.1.173
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发表时间：
1976
期刊：
影响因子：
--
通讯作者：
L. Wattenberg
中科院分区：
文献类型：
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作者：
P. Borchert;L. Wattenberg
通过经口插管对雌性远系繁殖ICR/Ha小鼠给予苯并[a]芘（BP）30周后，在90%以上的给药动物中诱导前胃肿瘤形成。然而，如果将1%双硫仑添加到实验饮食中，则该部位不会发生肿瘤。这种肿瘤形成的抑制作用被前胃中[3 H]BP和[14 C]BP与RNA和蛋白质的大分子结合的大抑制所抵消。特异性结合的抑制作用在以8，000 X g分离20分钟的RNA级分中最强（是对照的6倍），而在DNA级分中最弱（无显著差异）。在以32，000 X g分离120分钟的RNA级分中测量到最高的特异性结合，并且在DNA级分中测量到最低的结合。BP结合的相对分布为大于90%的BP与蛋白质结合，小于1%与DNA结合。在所有研究的大分子种类的BP结合的总抑制中，对蛋白质的抑制构成了最大的成分（95%）。与前胃相反，在肝脏中没有发现双硫仑对BP与DNA、RNA或蛋白质结合的抑制作用，在所采用的实验条件下，肝脏仍然没有癌症。
Benzo[a]pyrene (BP) administered to female outbred ICR/Ha mice by oral intubation induced neoplasia in the forestomach after 30 weeks in more than 90% of treated animals. However, no tumors occurred at that site if 1% disulfiram was added to the experimental diet. This inhibition of tumor formation was paralleled by a large inhibition of macromolecular binding of [3H]BP and [14C]BP to RNA and protein in the forestomach. The inhibitory effect of specific binding was strongest in the RNA fraction isolated at 8,000 X g for 20 minutes (6 times that of the control) and weakest in the DNA fraction (no significant difference). The highest specific binding was measured in the RNA fraction isolated at 32,000 X g for 120 minutes and the lowest binding in the DNA fraction. The relative distribution of the BP binding was such that greater than 90% of the BP was bound to protein and less than 1% was bound to DNA. Of the total inhibition of BP binding to all the macromolecular species studied, that to protein constituted the largest component (95%). In contrast to the forestomach, no inhibitory effect of BP binding to DNA, RNA, or protein by disulfiram was found in the liver, which remained free of cancer under the experimental conditions employed.