The chromosome constitution of CHEF/16 clones recovered from methylcellulose and of uncloned, tumor-derived CHEF/16 populations are compared. Nine of 11 clones recovered from methycellulose were initiated by diploid cells. Moreover, chromosomally diploid cells were still present in most CHEF/16 clones even after growth in anchorage-independent conditions. In contrast, none of the CHEF/16 cells recovered from tumors were diploid. Nonrandom chromosome changes were observed, but no specific chromosome alterations were consistently found in tumor-derived CHEF cells. Although CHEF/16 cells are uniformly tumorigenic in nude mice, each of 10 uncloned tumor-derived populations from inocula of 10(2), 10(4), and 10(6) CHEF/16 cells consisted of only 1-3 stemlines. Our results show that diploid CHEF/16 cells are premalignant and undergo karyotypic changes leading to successful and usually clonal establishment of tumors in nude mice.
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