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The DESCRIPTION (from the application) invention in this section focuses on the ability of known toxins to make cells enter mitosis in cell cultures. Although toxins are generally toxic to cells, they have been found to cause cells to enter mitosis and thus, to proliferate. For example, in a cell culture of N1E-115 neuroblastoma cells, a mouse neuroblastoma cell line, the neuropeptide, neurotensin, can cause the cells to exit the G2 phase of the cell cycle and enter mitosis. See, 7.9.1.

The neurotensin-induced stimulation of DNA synthesis in cells of transformed and untransformed animal tissues will be examined in detail by means of several isolation procedures on tissues which are normally not mitogenically responsive to neurotensin. The nature of the mitogenic response of the tissue will be examined by microscopic examination of the cells under phase contrast, ultraviolet, and electron microscopes. Qualitative and quantitative analysis of cell-cycle-related enzymes, with particular attention to DNA polymerases and their inhibitors will be performed.

A target cell should be examined for its proliferative ability after it has been exposed to toxin by addition of a fluid containing toxin. This target cell should preferably be a cell which is not normally proliferative in the absence of the toxin. While the target cells of this invention will be neuronal cells, any cell can be the target cell of this invention. The neurotoxin can be added to the medium or placed near the target cells for hours to several days. The target cells can be dissociated or trypsinized prior to the addition of neurotoxin, and then re-plated in the presence of neurotoxin.

One of the methods to determine whether a target cell is responsive to the neuropeptide toxin is to add the neurotoxin to the medium and to determine the effect of the toxin on the target cell. The target cell can be labeled with tritiated thymidine during a period when the target cell is in G2 phase of the cell cycle and then placed in the presence of the toxin. If the toxin causes the target cell to enter mitosis, the target cell will incorporate the radioactive thymidine which is found in normal DNA. This

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