Spiegelman S, Baxt W, Kufe D, Peters W P, Schlom J
Bibl Haematol. 1975(40):3-25. doi: 10.1159/000397514.
DNA-RNA hybridization was used to explore whether human neoplasias contain RNA molecules having sequence homologies to those of the RNA tumor viruses known to cause similar diseases in animals. The pattern of specific RNAs found in the human tumors showed a remarkable concordance with the predictions deducible from the animal systems. Thus human breast cancer contains RNA homologous only to that of the murine mammary tumor virus (MMTV). Human leukemias, sarcomas, and lymphomas (including Hodgkin's and Burkitt's) all contain RNA with sequence homology to the murine leukemia virus (RLV) and not to MMTV RNA. Finally, as in the case of the mouse, none of the human tumors examined contain RNA related in sequence to that of the avian myeloblastosis virus (AMV). The RNA detected in all of the human neoplasias was demonstrated to be of high molecular weight (1 times 10(7) daltons) and encapsulated with a reverse transcriptase in particles having densities between 1.16-1.19 g/ml. Further, the RNA of these human tumor particles was related in sequence to the murine viruses that cause the corresponding neoplasias in mice. Thus, 4 features diagnostic for the murine oncogenic viruses are satisfied by the particles found in the human cancers. Finally, it was shown by "recycling" experiments that the DNA from human leukemic cells and from lymphomatous tissue contained particle-related sequences that could not be detected in normal DNA. This finding was further substantiated by studies with identical twins in which it was shown that the leukemic twin contained particle-related sequences that could not be detected in the leukocytes of his identical healthy sibling. These findings are inconsistent with hypotheses that require chromosomal transmission in the germ line of complete copies of the information required to produce malignancy and the associated virus particles.
DNA - RNA杂交技术被用于探究人类肿瘤是否含有与已知能在动物中引发类似疾病的RNA肿瘤病毒具有序列同源性的RNA分子。在人类肿瘤中发现的特定RNA模式与从动物系统中推导出来的预测结果显示出显著的一致性。因此，人类乳腺癌仅含有与鼠乳腺肿瘤病毒（MMTV）的RNA同源的RNA。人类白血病、肉瘤和淋巴瘤（包括霍奇金淋巴瘤和伯基特淋巴瘤）均含有与鼠白血病病毒（RLV）具有序列同源性的RNA，而与MMTV RNA无同源性。最后，如同在小鼠中一样，所检测的人类肿瘤均不含有与禽成髓细胞瘤病毒（AMV）序列相关的RNA。在所有人类肿瘤中检测到的RNA被证明具有高分子量（1×10⁷道尔顿），并在密度为1.16 - 1.19 g/ml的颗粒中与逆转录酶一起被包裹。此外，这些人类肿瘤颗粒的RNA在序列上与在小鼠中引发相应肿瘤的鼠病毒相关。因此，人类癌症中发现的颗粒满足了对鼠致癌病毒的4个诊断特征。最后，通过“循环”实验表明，来自人类白血病细胞和淋巴瘤组织的DNA含有在正常DNA中无法检测到的与颗粒相关的序列。对同卵双胞胎的研究进一步证实了这一发现，结果表明患白血病的双胞胎含有在其健康的同卵兄弟姐妹的白细胞中无法检测到的与颗粒相关的序列。这些发现与那些要求在种系中通过染色体传递产生恶性肿瘤及相关病毒颗粒所需全部信息的假说不一致。
