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Tumorigenicity in the Nude Mouse of Cocultures Derived from Two Nontumorigenic Cell Types, Human Pituitary Adenomas and Mouse C3H 10T1/2 Fibroblasts

Division of Neurosurgery, University of California, San Diego Medical Center, San Diego, California 92103, and The Veterans Administration Medical Center, La Jolla, California 92161.

Human pituitary adenoma tissues were not tumorigenic in the hormonally manipulated nude mouse. Mouse fibroblast cells (C3H 10T1/2) also did not form tumors when inoculated alone into nude mice. When these two tissues were cocultured and coinoculated into nude mice however, the majority of inocula developed progressively enlarging tumors which could be established in tissue culture and passaged through the nude mouse. These tumors were sarcomatous histologically and thus did not resemble any human pituitary adenoma tissue injected. In order to detect any human cells in these tumors, tumor genomic DNA was subjected to Southern analysis using human repetitive Alu and HGH DNA sequence probes. Southern blot analysis of the nude mouse derived tumor genomic DNA revealed no sizeable human DNA in the mouse tumor cell genome indicating the absence of significant numbers of human cells in the tumors or the transfer of human DNA to the mouse cells. The tumors therefore arose from transformed C3H 10T1/2 cells after coculture with the human pituitary adenoma cells. These results implied that the tumorigenic transformation of susceptible C3H 10T1/2 cells in the cocultures occurred as a result of the secretion by the adenoma cells of transforming substances in the culture media or the induction of tumorigenicity through direct cell-cell contact between the two cell types.

¹ Supported by a research grant from the Veterans Administration (H.S.U) and a Teacher Investigator Development Award (H.S.U) from the National Institutes of Health. To whom requests for reprints should be addressed, at Division of Neurosurgery, H-893, University of California, San Diego Medical Center, 225 Dickinson Street, San Diego, CA 92103.

Received 8/ 5/86. Revised 5/13/87. Revised 7/22/87. Accepted 7/24/87.