Isolation of a Cellular Subpopulation from a Human Colonic Carcinoma Cell Line

A population of cells with increased resistance to 5-fluorouracil was isolated from cultures of the human colonic carcinoma cell line HT29. The resistant cells (HTFU) showed an altered morphology by light and electron microscopy and demonstrated contact inhibition in vitro. DNA assays and chromosome counts showed that HT29 cultures exhibit both hyper-and hypoaneuploidy, while HTFU cultures appear exclusively hypoaneuploid. One year after the isolation of HTFU, both cell lines showed equal sensitivity to 5-fluorodeoxyuridine while HTFU cells retained comparative insensitivity to 5-fluorouracil. Carcinoembryonic antigen production was not demonstrated in pre-or postconfluent cultures of HTFU, although carcinoembryonic antigen was present in both cells and media of HT29 cultures. Growth in semisolid medium was demonstrated for both cultures; however, HTFU showed a lower plating efficiency than did HT29. Tumors were observed in all of the nude mice given injections of HT29 or HTFU cells. Tumors formed from HTFU cells were smaller, and frequently the primary site receded after 6 to 8 weeks. Although in vitro tests suggested a reduced tumorigenic potential for HTFU cells, metastasis was observed only in mice given injections of cells from the HTFU line.