In situ identification of host derived infiltrating cells in chemically induced fibrosarcomas of interspecific chimeric mice

Abstract

Chimeric mice have been used to investigate the cellular origin of chemically induced tumors. Interspecific chimeras were formed between the Ha/ICR strain of Mus musculus and Mus caroli. The normal tissues of the chimeric mice were composed of a mixture of cells which originated from each of the 2 species. The species of origin of the cells was determined both histologically with in situ hybridization using a DNA probe which recognizes M. musculus satellite DNA and by electrophoretic analysis of phosphoglycerate kinase‐I (PGK‐I) isozyme expression. The 2 parental species, M. musculus and M. caroli, had comparable levels of inducible cytochrome P‐450‐dependent mixed function oxidase activity. Subcutaneous fibrosarcomas were induced with 3‐methylcholanthrene. Electrophoretic analysis of many samples from the tumors revealed that some demonstrated both isozymes of PGK‐I. However, extensive sectioning with subsequent in situ hybridization revealed that the only cells of mixed genotype were small, infiltrating inflammatory cells. These results confirmed PGK‐I analysis of the tissue culture cell lines derived from the tumors. This is the first report of direct visualization of the lineage origin of various cellular components in chemically induced tumors in a mosaic system and supports the contention that, while the neoplastic cells are clonal in origin, the tumors also contain non‐neoplastic “host” cells which are derived from both sets of parents.