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Developmental potential of myeloid leukemia cells injected into midgestation embryos.

Cells from a clone of mouse myeloid leukemic cells that can be induced to differentiate in vitro to mature cells by the normal macrophage- and granulocyte-inducing protein, MGI-2, were injected into mouse embryos at 10 days gestation. The leukemic cells, derived from an SJL/J mouse, were microinjected into the placentae of C3HeB fetuses and the viable progeny were tested for chimerism by analysis of glucose phosphate isomerase isozymes. Fifty-five percent out of 201 viable progeny died prior to weaning due to tumors derived from the injected cells. Of the remaining 91 apparently healthy adult animals, 2 had chimeric populations. One mouse had a chimeric population of granulocytes and the other mouse a chimeric population of macrophages. The animal with a chimeric population of macrophages was chimeric at 1 and 2 months of age and had lost any detectable donor derived contribution by the age of 3 months. The chimeric granulocyte population in the other animal was still stable at 3 months. The myeloid leukemic cells injected into midgestation embryos thus participated in the development of two different cell types in apparently healthy adult animals. Our results indicate that malignant cells of more restricted developmental potential than teratocarcinoma cells may participate in normal development. It remains to be determined whether this participation in normal development was due to normal differentiation of the malignant cells, or the production of nonmalignant segregants derived from the malignant cells.

Animals↗

Stable genotypic composition of blood cells in allophenic mice derived from congenic C57BL/6 strains.

Random shifts in blood cell genotypic composition are commonly observed in allophenic mice. This phenomenon was studied in 16 mosaic mice produced from very closely related strains, and no such changes were observed in the mosaic composition of erythrocytes, platelets, and lymphocytes over a period of 14 weeks. Furthermore, the mosaic distribution of a large group (66) of these mosaic mice was markedly biased in favor of those animals containing major contributions of both strains. This contrasts with what is normally found in collections of allophenic mice, in which the mosaic distribution curves are usually much flatter. While most allophenic mice have been produced from inbred strains with many genetic differences our results were obtained with congenic strains. This suggests that both properties, the unstable mosaic composition of blood cells and the flat mosaic distribution curves, are caused by specific genetic differences between cells of the two strains and are not inherent properties of allophenic mice. We propose that genetic differences cause these phenomena by inhibiting the mixing of cells of the two strains. Such might occur for example if, throughout development, cells of the same H-2 haplotype had greater affinity for each other than for ones of disparate H-2 haplotypes.

Animals↗

Entamoeba histolytica: effect of growth conditions and bacterial associates on isoenzyme patterns and virulence.

In xenic culture, isolates of Entamoeba histolytica from asymptomatic carriers are characterized, with rare exception, by possession of a nonpathogenic zymodeme. During the process of axenizing such an isolate, strain CDC:0784:4, a change in the pattern of the isoenzymes from nonpathogenic zymodeme I to pathogenic zymodeme II was observed 40 days after the amebae had been transferred from a medium for xenic cultivation to one used for axenic cultivation, but before axenization of the amebae had actually occurred. Axenization was accomplished by feeding the amebae lethally irradiated bacteria while suppressing and finally eradicating with antibiotics the bacterial flora accompanying the amebae in the original xenic culture. The change in zymodeme was accompanied by a change in virulence as evidenced by the ability of the amebae to produce hepatic abscesses in hamsters and to destroy monolayers of tissue culture cells. Two explanations are offered for the observed changes in zymodeme and virulence: a zymodeme is not a stable inherent property of the ameba. Alternatively, the original isolate consisted of two zymodeme populations and the conditions of growth selected for one or the other of the populations. In either case, our results suggest that the finding of a particular zymodeme in a culture of E. histolytica isolated from an asymptomatic carrier of the parasite cannot be used to predict a clinical condition or serve as a basis for the recommendation of therapy.

Amebiasis↗