Pure-Strain and Genetically Mosaic Liver Tumors Histochemically Identified with the β -glucuronidase Marker in Allophenic Mice

A histochemical procedure for β-glucuronidase has been used to make visible the cellular genotypes of liver tumors and of surrounding normal liver clones in allophenic mice. The animals had lifelong genetic mosaicism for cells with the allele for low β-glucuronidase activity (g/g genotype, C3H strain) and cells with the allele for high activity (G/G genotype, C57BL/6 or BALB/c strain). The former strain is also hepatoma-susceptible; both the latter are nonsusceptible. Of 12 "spontaneous" hepatomas examined, nine were entirely of susceptible-strain hepatic cells and one was of the nonsusceptible strain; the pure-strain tumors usually arose in a liver environment containing clones of each genotype. The cells therefore behave largely autonomously with respect to gene control of tumor susceptibility. However, two tumors with malignant cells of both genotypes were formed, which suggests some measure of intercellular transmission of tumor information. Alternatively, transformation might have occurred in two or more cells concurrently. Mosaic tumors in either case imply that even a hepatoma of one inbred strain, whether in a single-genotype animal or an allophenic mouse, may comprise diverse clones of transformed cells. Possibly many or all hepatomas may therefore be genetically complex entities.