SUPPRESSION OF TUMORIGENICITY IN HUMAN COLON-CARCINOMA CELLS BY INTRODUCTION OF NORMAL CHROMOSOME-5 OR CHROMOSOME-18

DEVELOPMENT of colon carcinomas can be associated with allelic deletions on several chromosomes, including 5q and 18q (refs 1-10). The APC gene11-13 on 5q and the DCC gene14 on 18q have been identified as potential tumor suppressor genes, whose suppression contributes to colon carcinogenesis. To investigate the role of genes in these deleted regions, we have now introduced a single normal human chromosome into a human colon carcinoma cell line, COKFu, through microcell hybridization15-20. Several clones of hybrid cells containing normal chromosome 5, and others containing normal chromosome 18, were obtained. The morphology of the hybrid cells was markedly altered: the hybrids with chromosome 5 exhibited a closely packed polygonal morphology, and the hybrid cells with chromosome 18 were flattened. The cloning efficiency of the hybrid cells in soft agar was reduced from 0.46 to 0% of that of the parental carcinoma cells, and the tumorigenicity of these hybrid cells in athymic nude mice was completely suppressed. The growth properties of the hybrid cells with chromosome 11 were not substantially changed. These results strongly suggest that the genes on normal chromosome 5 and 18 function as tumor suppressors in colon carcinogenesis.