Preliminary findings indicate that human cervical carcinoma cells of the D98AH2 (D98) cell line, derived from HeLa cells, contain high levels of mRNA of several oncogenes. Hybrids of D98 cells fused with normal human diploid cells initially contain all or most of the chromosomes of both parental cells and make much less mRNA of some of these oncogenes than the D98 cells do. When these hybrids lose chromosomes they again contain elevated levels of mRNA of these oncogenes. One chromosome No. 11 of the diploid parent has almost always been lost from these hybrids, as indicated by DNA restriction fragment length polymorphic chromosome marker studies, and they have often also lost copies of the No. 2, the cell parental origin of which has not yet been determined. These results suggest that information of specific chromosomes of the normal cell may affect transcription of oncogenes. The objective of this study is to determine if genetic information on specific chromosomes affects oncogene transcription. We will conduct segregation analysis of appropriate panels of cell hybrids and identify chromosomes that affect the level of transcription of oncogenes to determine if the postulated regulators are on the same chromosomes as the structural loci of the oncogenes whose expression they control. To determine if the findings in hybrids made with the long established D98 cells are represenative of oncogene regulation in other cells, they will be compared with results from hybrids that will be made with a recently isolated human cancer cell line. These cells have a single chromosome rearrangement with an otherwise normal chromosome complement. (X)
