Probable Clonal Development of Foreign-Body-Induced Murine Sarcomas

Abstract

The number of cells from which tumors induced by subcutaneous implantation of foreign bodies develop was studied in BALB/c mice with X-chromosome-inactivation mosaicism. Because only one of the two X-chromosomes is active in XX somatic cells, a female mouse heterozygous at the X-linked phosphogly-cerate kinase (PGK) locus for Pgk-1^b and Pgk-1^a has two types of cells. In one population Pgk-1^b is active and B-enzyme is produced, whereas in the other population Pgk-1^a is active and A-type enzyme is synthesized. Normal tissues from these mosaic mice display both enzyme types, but a tumor that develops from a single cell exhibits only one of the two PGK enzyme types. Of 11 sarcomas induced by Millipore filters, 8 showed single-enzyme PGK phenotypes in primary tumors and in tissue cultures derived from them. The 3 other primary sarcomas showed double-enzyme phenotypes. However, transplantation of cultured cells from 2 of these sarcomas resulted in tumors with single-enzyme PGK phenotypes. Thus the data provide confirmatory evidence for the suggestion that most foreign-body-induced sarcomas develop clonally or from a relatively few cells.