NORMAL HUMAN-CHROMOSOME-2 INDUCES CELLULAR SENESCENCE IN THE HUMAN CERVICAL-CARCINOMA CELL-LINE SIHA

For identification of the chromosome carrying cellular senescence-indu cing activity, normal human chromosome 2, 3, 6, 7, 9, 11, or 12 ragged with a selectable marker gene (neo) was introduced into the human cer vical carcinoma cell line SiHa via microcell-mediated chromosome trans fer. Seventy-six percent (158/207) of the G418-resistant clones obtain ed by the transfer of chromosome 2 showed a remarkable change in morph ology (cells were flat), and 93% (147/158) of them ceased to divide (s enesced) prior to 6-9 population doublings, whereas most of the clones generated by the transfer of other chromosomes exhibited a morphology similar to that of the parental cells and continued to grow. Chromoso me analyses suggested that cells which escaped from senescence contain ed only a small fragment derived from the transferred chromosome 2, wh ereas the transferred chromosomes were apparently intact in most of th e continuously growing microcell hybrids with introduction of other ch romosomes. These results indicate that the normal human chromosome 2 c arries a gene or genes that induce cellular senescence in SiHa cells. (C) 1995 Wiley-Liss, Inc.