Reddy A L, Fialkow P J
J Exp Med. 1979 Oct 1;150(4):878-87. doi: 10.1084/jem.150.4.878.
The cellular origin of tumors induced by the chemical carcinogen 3-methylcholanthrene (MCA) was studied in mice with X-chromosome inactivation mosaicism. Because only one of the two X-chromosomes is active in XX somatic cells, a female heterozygous at the X-linked phosphoglycerate kinase (PGK-1) locus for the usual Pgk-1b gene and the variant Pgk-1a has two populations of cells, in the cells of one population, Pgk-1b is active and B-type enzyme is synthesized, whereas in cells of the other population, A-type enzyme is produced. Both enzyme types are found in normal tissues from these mosaic mice. A tumor developing from a single cell exhibits only one of the two PGK enzyme types, whereas a tumor with a multicellular origin expresses both enzymes (i.e., it has a double-enzyme phenotype). Five fibrosarcomas developing at the site of injection of 0.2 or 2.0 mg of MCA were analyzed. 36 of 38 fragments from the five tumors had double-enzyme PGK phenotypes. One piece from each of two tumors showed a single-enzyme phenotype. Histological, cell culture, and cloning studies indicate that the double-enzyme phenotypes reflect the presence of both types of malignant cells and not admixture of normal with neoplastic elements in the specimens tested for PGK. The results suggest strongly that these fibrosarcomas have a multicellular origin.
利用X染色体失活嵌合体小鼠研究了化学致癌物3-甲基胆蒽（MCA）诱导肿瘤的细胞起源。因为在XX体细胞中两条X染色体只有一条是活跃的，所以在X连锁磷酸甘油酸激酶（PGK-1）位点杂合的雌性小鼠，对于常见的Pgk-1b基因和变异的Pgk-1a基因来说，有两类细胞群体。在其中一类细胞群体中，Pgk-1b是活跃的，合成B型酶；而在另一类细胞群体中，产生A型酶。在这些嵌合体小鼠的正常组织中能发现这两种酶类型。由单个细胞发育而来的肿瘤只表现出两种PGK酶类型中的一种，而多细胞起源的肿瘤则表达两种酶（即具有双酶表型）。分析了在注射0.2或2.0毫克MCA的部位产生的5个纤维肉瘤。这5个肿瘤的38个片段中有36个具有双酶PGK表型。两个肿瘤各有一个片段显示单酶表型。组织学、细胞培养和克隆研究表明，双酶表型反映了两种类型恶性细胞的存在，而不是在检测PGK的标本中正常成分与肿瘤成分的混合。结果强烈表明这些纤维肉瘤具有多细胞起源。
