Development and Progression of Karyotypic Variability in Melanoma K1735 following X-Irradiation

Chromosomal aberrations are often assumed to be deleterious to cells. However, we have found that many metastases are populated by cells with chromosomal recombinants induced by radiation of the original tumor population. The tumor, K-1735-M2, was already capable of metastasis so that the recombinant chromosomes were not necessary for this property of the tumor. Stable recombinants, like other aberrant forms, could be disadvantageous or, alternatively, could confer selective advantage to some tumor cells. We investigated these possibilities by irradiating the parental tumor line and examining the formation and persistence of chromosomal markers in cell culture and in s.c. tumors. The karyotype of the K-1735-M2 parental tumor is composed entirely of telocentric chromosomes, and recombinant forms are relatively easy to recognize. Unstable forms of chromosome damage were lost rapidly. The frequency of stable recombinants after two weeks in culture was higher than that in tumors growing in primary inoculation sites. In contrast, secondary (spontaneous metastatic) foci showed a far greater frequency of chromosomal markers, suggesting a positive association between markers and acquisition of properties benefiting growth and metastasis.