Abstract
We have used irradiation to induce marker chromosome formation in a metastasizing murine tumor with a stable karyotype. The induced recombinant chromosomes then served to determine whether metastases were of clonal or multicellular origin. Cumulative data were obtained from four series of experiments on spontaneous metastases originating from tumors grown from irradiated cells; 20 of these metastases expressed unique chromosomal alterations consistent with a clonal origin. The majority of metastasis-derived cell populations remain stable with respect to their marker chromosomes in culture as well as in successive animal transplantation. In several instances, however, chromosomal instability was sufficient to obscure the cellular origins of individual metastases. A few metastases showed mixed chromosomal patterns initially that were consistent with multicellular origin, but repeat examinations have revealed a chromosomal instability which persisted during propagation in culture.
The frequency of chromosomal recombinants in metastases from the combined series was sufficient to suggest biological and statistical significance. The morphology of recombinants was not associated with radiation dose but appeared as an apparently random response of the tumor population in different experiments. Analysis of chromosomal markers by banding techniques was performed to determine if specific chromosomes or chromosomal sites were associated with tumor cells from metastatic foci (a host-selected subpopulation with a metastatic phenotype). Our results did not reveal preferential involvement of whole chromosomes or intrachromosomal sites in recombinant formation.
This research was sponsored by the Biological Resources Branch, Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, Department of Health and Human Services, under Contract N01-23910 with Program Resources, Inc. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. By acceptance of this article, the publisher or recipient acknowledges the right of the United States Government to retain a nonexclusive, royalty-free license in and to any copyright covering the article.