Weinberg W C, Berkwits L, Iannaccone P M
Carcinogenesis. 1987 Apr;8(4):565-70. doi: 10.1093/carcin/8.4.565.
The clonality of tumors has been convincingly established. Because it is generally accepted that tumor formation involves a number of steps, it is important to determine which if any of the precursors of tumors are clonal. A series of chimeric rats produced between congenic strains by morulae aggregation were used to establish the cellular composition of foci of gamma-glutamyl transpeptidase (gamma-GTP; E.C. 2.3.2.2) expression in liver following initiation with N-nitrosodiethylamine and promotion with phenobarbital. The chimeras were produced between congenic rat strains (PVG and PVG-RT1a) genetically distinguished by alleles of the major histocompatibility complex (MHC). Monoclonal antibodies directed to distinctive class I MHC alloantigens were used to detect patterns of mosaicism in the animals. The parental genotypes present in most visceral tissues could be easily distinguished by our method. Analysis of 499 enzyme-altered foci revealed that 474 were comprised solely of either PVG-RT1a or PVG cells. Some apparent mixture of cells from the two lineages was observed in 25 lesions, most of which were very small. The observed pattern of distortion of normal patch distribution clearly indicated the expanding and clonal nature of these lesions.
肿瘤的克隆性已得到令人信服的确立。由于人们普遍认为肿瘤形成涉及多个步骤，所以确定肿瘤的任何前体是否为克隆性是很重要的。通过桑葚胚聚集在同基因品系之间产生的一系列嵌合大鼠，被用于确定在经N-亚硝基二乙胺启动并用苯巴比妥促进后，肝脏中γ-谷氨酰转肽酶（γ-GTP；E.C. 2.3.2.2）表达灶的细胞组成。嵌合体是在由主要组织相容性复合体（MHC）等位基因遗传区分的同基因大鼠品系（PVG和PVG-RT1a）之间产生的。针对独特的I类MHC同种异体抗原的单克隆抗体被用于检测动物中的镶嵌模式。通过我们的方法可以很容易地区分大多数内脏组织中存在的亲代基因型。对499个酶改变灶的分析显示，474个仅由PVG-RT1a或PVG细胞组成。在25个病变中观察到了来自两个谱系的细胞的一些明显混合，其中大多数非常小。观察到的正常斑块分布的扭曲模式清楚地表明了这些病变的扩张性和克隆性。
