BIOLOGY

Questions and Answers

Questions and Answers

Question 1)

A. Retrovirus DNA is stably integrated in host cell DNA. However, little is known about the sites of integration and the mechanism by which viral DNA integrates into host cell DNA. Early after retrovirus infection of sensitive cells, many complete viral DNA molecules are synthesized and some are also found in the nucleus. Only a portion of these molecules become stably integrated in the host genome (2-5). The reason for the restricted number of integrated viral DNA molecules is unknown. Rat hepatoma cells infected with mouse mammary tumor virus (MMTV) acquire viral DNA that becomes covalently linked to the cell DNA. Using restriction endonucleases and the DNA transfer procedure of Southern, we have studied the sites in cellular DNA into which MMTV DNA inserts. These experiments indicate that: (i) there are many sites in cell DNA into which MMTV DNA integrates; (ii) the junctions between viral and cellular DNA occur within a limited portion of the viral genome; (iii) clones that contain MMTV DNA do not necessarily produce viral RNA; and (iv) the extent of transcription and glucocorticoid responsiveness of MMTV pro-viruses may be dependent on the site(s) in cell DNA in which the viral DNA resides.

B. We have over the past few years focused our efforts on an attempt to determine whether the knowledge gained from animal viral oncology is relevant to the etiology of human cancer. We first searched in human tumors for RNA molecules related in sequence to those found in the RNA tumor viruses known to cause corresponding cancers in experimental animals. Radioactive DNAs synthesized on the appropriate viral RNA templates with RNA-directed DNA polymerase were used as probes. The data obtained revealed a pattern of specificities that agreed remarkably with what was known from the animal experimental systems. Human breast carcinomas were found (1) to contain RNA homologous to that of the mouse mammary tumor virus. As expected, the human mammary tumor RNA showed no homology to that of the unrelated Rauscher leukemia virus. This observation gained in interest and significance when we turned our attention to human leukemias (2), sarcomas (3), and lymphomas (4). Here we found RNA homologous to that of the Rauscher leukemia virus, an agent related to a group that causes similar neoplasias in mice.

C. Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as malignant degeneration of a previously existing benign tumor. There are many causes of primary malignant transformation, or tumorigenesis. The underlying commonality is genetic mutation either by inheritance or more commonly by acquiring mutations in one's DNA over time. Although malignant transformation may occur because of changes within the cell, it can be induced by inorganic toxic substances such as cadmium or arsenite and organics such as tobacco-specific nitrosamines. It is also thought that some malignant transformations are due to viruses such as the Epstein-Barr virus, although this is currently restricted to just a few cancer ...