Kimball P C, Simon M C, Mishra N K
Proc Natl Acad Sci U S A. 1980 Jun;77(6):3450-4. doi: 10.1073/pnas.77.6.3450.
Cultured rat embryo cells are resistant to neoplastic transformation by chemical carcinogens unless they are extensively subcultured or infected with a murine leukemia virus (MuLV) first. We found that, in normal cultured cells, MuLV activates expression of rat genes that are the progenitors of sarcoma virus genes, but not those of endogenous "leukemia" virus. Elevated levels of sarcoma virus-related RNA in normal cells infected with MuLV were indistinguishable from the levels in cells transformed spontaneously or by a carcinogen or a sarcoma virus. Because of previous reports that some carcinomas in rats also contain elevated levels of sarcoma virus-related RNA, we believe these events can be explained by a molecular genetic model which may be generally valid for initiation of carcinogenesis. The basic elements of the model are: transcriptional activation of all the multiple copies of normal rat progenitors of sarcoma virus genes is required before cellular transformation can be initiated, and initiation occurs when a spontaneous or induced mutation in any one active copy of these same genes generates a dominant transforming function.
培养的大鼠胚胎细胞对化学致癌物诱导的肿瘤转化具有抗性，除非它们首先被大量传代培养或感染鼠白血病病毒（MuLV）。我们发现，在正常培养的细胞中，MuLV会激活大鼠基因的表达，这些基因是肉瘤病毒基因的前身，但不会激活内源性“白血病”病毒的基因。感染MuLV的正常细胞中肉瘤病毒相关RNA水平的升高与自发转化或由致癌物或肉瘤病毒转化的细胞中的水平没有区别。由于之前有报道称大鼠中的一些癌组织也含有升高水平的肉瘤病毒相关RNA，我们认为这些事件可以用一种分子遗传模型来解释，该模型可能普遍适用于肿瘤发生的起始阶段。该模型的基本要素是：在细胞转化开始之前，需要对肉瘤病毒基因的所有多个正常大鼠前身拷贝进行转录激活，并且当这些相同基因的任何一个活性拷贝发生自发或诱导突变产生显性转化功能时，转化就会发生。
