A GENE INVOLVED IN CONTROL OF HUMAN CELLULAR SENESCENCE ON HUMAN CHROMOSOME-1Q

Normal cells in culture exhibit limited division potential and have be en used as a model for cellular senescence. In contrast, tumor-derived or carcinogen- or virus-transformed cells are capable of indefinite d ivision. Fusion of normal human diploid fibroblasts with immortal huma n cells yielded hybrids having limited life spans, indicating that cel lular senescence was dominant. Fusions of various immortal human cell lines with each other led to the identification of four complementatio n groups for indefinite division. The purpose of this study was to det ermine whether human chromosome 1 could complement the recessive immor tal defect of human cell lines assigned to one of the four complementa tion groups. Using microcell fusion, we introduced a single normal hum an chromosome 1 into immortal human cell lines representing the comple mentation groups and determined that it caused loss of proliferative p otential of an osteosarcoma-derived cell line (TE85), a cytomegaloviru s-transformed lung fibroblast cell line (CMV-Mj-HEL-1), and a Ki-ras+- transformed derivative of TE85 (143B TK-), all of which were assigned to complementation group C. This chromosome 1 caused no change in prol iferative potential of cell lines representing the other complementati on groups. A derivative of human chromosome 1 that had lost most of th e q arm by spontaneous deletion was unable to induce senescence in any of the immortal cell lines. This finding indicates that the q arm of human chromosome 1 carries a gene or set of genes which is altered in the cell lines assigned to complementation group C and is involved in the control of cellular senescence.