More than one-third of the discernible mouse polypeptides are not expressed in a Chinese hamster-mouse embryo fibroblast hybrid that retains all mouse chromosomes.

Gene expression at the level of polypeptide synthesis has been investigated in a somatic cell hybrid (20 BW-4) isolated after fusion of spontaneously transformed, tumorigenic Chinese hamster lung fibroblasts with mouse embryo fibroblasts. This hybrid exhibited suppression of tumorigenicity and retained--in addition to the parental Chinese hamster genome--copies of all mouse chromosomes as demonstrated by direct karyotype analysis and confirmed for 18 different mouse chromosomes by analysis of 18 different mouse isozymes. Two-dimensional gel electrophoresis of [35S]methionine-labeled polypeptides from hybrid 20 BW-4 showed that the overall polypeptide pattern corresponded to that of the hamster parent. All polypeptides detected in the hamster parental cells were also expressed in the hybrid although some of them were expressed in altered amounts. Of approximately 1200 labeled polypeptides revealed in the parental cells, 115 mouse polypeptides could be clearly distinguished from the hamster polypeptides due to their different electrophoretic mobilities. Forty-two of these (i.e., 37%) were not expressed in the hybrid 20 BW-4. These observations were confirmed by analysis of another independently isolated hybrid (2W 23) of the same parental cells that also exhibited suppression of malignancy and that retained copies of all mouse chromosomes except no. 5. The results suggest that the genome of the tumorigenic cell after hybridization can suppress expression of more than one-third of the normal parental genome. The suppressed mouse genetic information is probably located on many, if not all, different mouse chromosomes. Even if the level of genetic suppression is high the mouse genome is able to reduce the tumorigenicity of the hamster parental cell.