Borchert P, Wattenberg L W
J Natl Cancer Inst. 1976 Jul;57(1):173-9. doi: 10.1093/jnci/57.1.173.
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.
通过口服插管给雌性远交群ICR/Ha小鼠施用苯并[a]芘（BP），30周后，超过90%的受试动物前胃发生肿瘤。然而，如果在实验饮食中添加1%的双硫仑，则该部位不会出现肿瘤。肿瘤形成的这种抑制与前胃中[3H]BP和[14C]BP与RNA和蛋白质的大分子结合的大幅抑制同时出现。特异性结合的抑制作用在以8000×g离心20分钟分离的RNA组分中最强（是对照的6倍），在DNA组分中最弱（无显著差异）。在以32000×g离心120分钟分离的RNA组分中测得的特异性结合最高，在DNA组分中结合最低。BP结合的相对分布情况是，超过90%的BP与蛋白质结合，不到1%与DNA结合。在对所有研究的大分子物种的BP结合的总抑制中，对蛋白质的抑制构成最大部分（95%）。与前胃相反，在肝脏中未发现双硫仑对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未发生癌变。
