Multicellular origin of fibrosarcomas in mice induced by the chemical carcinogen 3-methylcholanthrene.
Multicellular origin of fibrosarcomas in mice induced by the chemical carcinogen 3-methylcholanthrene.
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DOI：
10.1084/jem.150.4.878
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发表时间：
1979-10-01
期刊：
影响因子：
--
通讯作者：
Fialkow PJ
中科院分区：
文献类型：
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作者：
Reddy AL;Fialkow PJ
本文用X染色体失活嵌合现象研究了化学致癌物3-甲基胆蒽（MCA）诱发小鼠肿瘤的细胞起源。因为在XX体细胞中两条X染色体中只有一条是活跃的，所以在X连锁磷酸甘油酸激酶（PGK-1）基因座上对于通常的Pgk-1b基因和变体Pgk-1a基因杂合的雌性具有两个细胞群体，在一个群体的细胞中，Pgk-1b是活跃的并且合成B型酶，而在另一个群体的细胞中，产生A型酶。这两种酶都存在于这些嵌合体小鼠的正常组织中。从单细胞发展的肿瘤仅表现出两种PGK酶类型中的一种，而具有多细胞起源的肿瘤表达两种酶（即，它具有双酶表型）。分析了5例在注射0.2或2.0 mg MCA部位发生的纤维肉瘤。5个肿瘤的38个片段中有36个具有PGK双酶表型。两个肿瘤中的每一个都显示出单酶表型。组织学、细胞培养和克隆研究表明，双酶表型反映了PGK检测标本中存在两种类型的恶性细胞，而不是正常细胞与肿瘤细胞的混合物。结果强烈提示这些纤维肉瘤具有多细胞起源。
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.