Identification of a single chromosome in the normal human genome essential for suppression of hamster cell transformation

Abstract

Normal human fibroblasts were fused to carcinogen-transformed baby hamster kidney (BHK) cells and found to be able to suppress the anchorage-independent transformed phenotype of the hamster cells. This suppression was not due to interspecies incompatibility, for transformation could be effectively expressed in hybrids if either the human or the BHK parent had initially been transformed by a dominantly acting viral genome. Upon growth of suppressed hybrids, loss of human chromosomes was accompanied by the re-expression of transformation. Karyotype analysis indicated that only human chromosome 1 was retained in all hybrids that were suppressed and was lost in all hybrids in which transformation was re-expressed. Cytological evidence for the presence or absence of chromosome 1 was confirmed by electrophoretic identification of the human isozyme for phosphoglucomutase 1. Clones re-expressing transformation were isolated from two suppressed hybrids and in both cases loss of suppression was accompanied by the loss of human chromosome 1. Thus, the maintenance of suppression in these cross-species hybrids appears to require the continued presence of normal human chromosome 1. These findings raise the possibility that the frequent involvement of human chromosome 1 in potentially inactivating aberrations in human tumors may reflect a suppressor role for this chromosome in human malignancy.