DNA CONTENT OF DYSPLASTIC LESIONS IN HUMAN AND RAT LIVER

我们通过细胞光谱的方法发现，有一小部分 启动-促进方案诱导的大鼠肝结节 非整倍体模式DNA含量。在过去的两年里，我们不仅 证实了最初的发现，但也确定了非整倍体是 当给予胆碱缺乏或苯巴比妥时出现 分别在用二乙基亚硝胺进行相同的起始处理后。我们 现在有初步证据，这将在未来得到验证 实验表明，单独给药二乙基亚硝胺或 喂食胆碱缺乏的饮食本身就会在一些人中产生非整倍体 酶改变了病灶。基因组中的数量变化 导致非整倍体实际上是进展期的表现 在转化为恶性肿瘤的过程中。因为非整倍体会导致 异质细胞群体，随后一些肿瘤的能力 转移可能是在致癌开始时决定的。 过程，而不是更晚，作为随后公开的更改的结果 恶毒。 细胞分光光度法是一种勉强、缓慢的方法。……的到来 计算机化的数字图像分析与完全自动化 我们在本申请中提出的系统，应该可以克服这些问题中的大多数 有问题。 我们的第二阶段调查首先将主要致力于 原计划进行的研究倍性之间关系的实验 分布、结节残留与肝癌的发生发展。治疗 这些动物已经在第一个资助周期中进行了表演。使用 使用计算机化的图像分析我们还将确定 非整倍体可见于促进治疗或 二乙基亚硝胺分别施药时。在…的最后一部分 我们将使用相同的方法检查我们的研究是否非整倍体 是由甲基-N-的使用引起的碎裂变化引起的 亚硝基-尿素/苯巴比妥或黄曲霉毒素B1/苯巴比妥或 产生异常或停滞的有丝分裂纺锤体，如己烯雌酚。 所提出的实验将有助于理解 大鼠肝脏在体内的进展(与培养中的细胞相反)和 可能导致对体内的限制较少但更真实的监管 肝细胞癌发生的检测。

We have found, by cytospectrophotometric methods, that a small number of rat liver nodules induced by an initiation-promotion regimen have an aneuploid modal DNA content. Over the past two years we have not only confirmed the initial finding, but also determined that aneuploidy is present when either choline deficiency or phenobarbital are given separately after the same initiation treatment with diethylnitrosamine. We now have preliminary evidence, which will have to be validated in future experiments, that the administration of diethylnitrosamine alone or the feeding of a choline deficient diet by itself produces aneuploidy in some enzyme altered foci. The quantitative alterations in the genome that result in aneuploidy are in fact a manifestation of the PROGRESSION stage during transformation into malignancy. Since aneuploidy results in a heterogeneous cell population, the subsequent ability of some tumors to metastasize may have been decided at the beginning of the carcinogenic process and not later, as a consequence of changes that follow overt malignancy. Cytospectrophotometry is a grudging, slow methodology. The advent of Computerized Digital Image Analysis, together with the complete automation of the system we propose in this application, should overcome most of these problems. The second phase of our investigations will be at first devoted mostly to the originally planned experiments to study the relationship between ploidy distribution, nodule persistence and hepatoma development. Treatment of these animals has already been performed in the first funding cycle. With the use of Computerized Image Analysis we will also determine whether aneuploidy is seen with either promoting treatment or with diethylnitrosamine when each is applied separately. In the last part of our studies we will examine, using the same methodology, whether aneuploidy is caused by clastogenic changes due to the administration of methyl-N- nitros-urea/phenobarbital or aflatoxin B1/phenobarbital or by agents that produce abnormal or arrested mitotic spindles, such as diethylstilbestrol. The experiments proposed will help to understand the mechanisms of PROGRESSION in the rat liver in vivo (as opposed to cells in culture) and may result in less restrictive but more veritable regulations for in vivo tests of hepatocarcinogenesis.