Meier H, Taylor B A, Cherry M, Buebner R J
Proc Natl Acad Sci U S A. 1973 May;70(5):1450-5. doi: 10.1073/pnas.70.5.1450.
We analyzed the relationship of genetic factors determining the expression of endogenous type-C RNA tumor viruses and other host-gene markers to tumorigenesis. A hybridization experiment was performed with mice of strains AKR/J and C57L, the first filial (F(1)) generation hybrids, the second filial (F(2)) generation hybrids, and the backcrosses to the two parental strains. The results demonstrated a highly significant and predictable association between the expression of complete infectious virus or the viral group-specific (gs) antigen in spleens of young mice and tumorigenesis later in life. Most of the tumors were thymic leukemia and reticulum sarcoma, but other mesenchymal, as well as epithelial, tumors were also observed. Tumors occurred preferentially in gs-antigen- or virus-positive mice of all crosses; in the C57L-backcross and F(2) mice segregating for gs-antigen and virus expression, a few gs-antigen-negative mice developed reticulum cell sarcomas. At the time of their occurrence, the mice were all gs-antigen-positive, and most had virus as well.A minor effect of the major histocompatibility locus, H-2, on leukemogenesis was found in the F(2) mice. Several tumor types were also found that we have never observed in the two parental strains. Our data provide the most direct biological evidence in favor of the viral oncogene theory. Thus, from the presence or absence of expression in early life of splenic gs antigen or virus, we can predict whether or not a tumor is likely to develop later in life. These findings suggest that the genome of endogenous type-C RNA viruses is the major determinant for tumorigenesis although they provide no clues about the factors responsible for the various histological types.
我们分析了决定内源性C型RNA肿瘤病毒表达的遗传因素及其他宿主基因标志物与肿瘤发生之间的关系。我们用AKR/J和C57L品系的小鼠、第一代（F(1)）杂交后代、第二代（F(2)）杂交后代以及与两个亲本品系的回交后代进行了杂交实验。结果表明，幼鼠脾脏中完整感染性病毒或病毒群特异性（gs）抗原的表达与后期的肿瘤发生之间存在高度显著且可预测的关联。大多数肿瘤为胸腺白血病和网状细胞肉瘤，但也观察到了其他间充质以及上皮性肿瘤。所有杂交组合中，肿瘤优先发生在gs抗原或病毒阳性的小鼠中；在C57L回交和F(2)小鼠中，gs抗原和病毒表达呈分离状态，少数gs抗原阴性的小鼠发生了网状细胞肉瘤。肿瘤发生时，小鼠均为gs抗原阳性，且大多数也携带病毒。在F(2)小鼠中发现主要组织相容性位点H-2对白血病发生有轻微影响。还发现了几种在两个亲本品系中从未观察到的肿瘤类型。我们的数据为支持病毒癌基因理论提供了最直接的生物学证据。因此，根据幼年期脾脏gs抗原或病毒表达的有无，我们可以预测后期是否可能发生肿瘤。这些发现表明，内源性C型RNA病毒的基因组是肿瘤发生的主要决定因素，尽管它们没有提供关于导致各种组织学类型的因素的线索。
