Monoclonal growth during chimeric mouse carcinogenesis demonstrated by a strain-specific antibody and microsatellite DNA polymorphism patterns.

用C3H株特异性抗原(CsA)的特异性抗体和微卫星DNA多态性研究了C3H/HEN**BALB/c嵌合小鼠结肠癌和前胃癌变相关的上皮增生性病变的克隆性。在嵌合体的正常结肠粘膜中，每个腺体均由CsA阳性或阴性细胞组成，未见混合腺。在每种情况下，嵌合体小鼠的所有局灶性非典型性细胞对于亲代类型中的一种或另一种都是同质的。在嵌合小鼠的91个腺瘤中，只有一个由两种类型的细胞组成。在119例腺癌中，12例同时含有两种亲本细胞。正常的嵌合前胃上皮显示由CsA阳性或阴性细胞组成的混合上皮细胞群。所有单纯性增生症都是如此。相反，许多PN增生性病变由CsA阳性和阴性细胞群组成。鳞状细胞癌全部由CsA阳性或阴性肿瘤细胞组成。然而，在多种晚期CsA阳性癌症和阴性癌症的动物中，发现由这两种亲本类型的细胞组成的癌巢是相关的。组织切片微卫星DNA多态图谱与免疫组织化学染色结果完全一致。结果表明，单个癌症是由表现出单克隆性生长的单个细胞分化而来的，而在进展过程中，由于两个或更多的病变合并，显然是继发的多克隆性肿瘤。

The clonality of epithelial proliferative lesions associated with colon and forestomach carcinogenesis was immunohistochemically investigated in C3H/HeN**BALB/c chimeric mice using a specific antibody to C3H strain specific antigen (CSA) and as well as in terms of microsatellite DNA polymorphism patterns. In normal colonic mucosa of the chimeras, each gland was composed entirely of either CSA positive or negative cells and no mixed glands were found. Cells of all focal atypias in chimeric mice were, in each case, homogeneous for one or other of the parental types. Of 91 adenomas in chimeric mice, only one comprised both types of cells. Among 119 adenocarcinomas, 12 contained cells of both parental types. Normal chimeric forestomach epithelium was found to demonstrate mixtures of epithelial cell groups composed of either CSA positive or negative cells. The same was the case for all simple hyperplasias. Many PN-hyperplasias, in contrast, consisted of both CSA positive and negative cell groups. Squamous cell carcinomas were composed entirely of either CSA positive or negative tumor cells. However in animals with multiple advanced CSA positive cancers and negative cancers, cancer nests composed of both parental type cells were found in association. Microsatellite DNA ploymorphism patterns sampled from histological sections completely conformed with the outcome of immunohistochemical staining. The results suggest that individual cancers are derived from single cells showing monoclonal growth, with apparently polyclonal tumors arising secondarily during progression, due to two or more lesions coalescing.