Growth and death of diploid and transformed human fibroblasts

Abstract

Three possible explanations are presented for the differences in growth potential between human diploid fibroblasts of finite life-span and permanent transformed lines: 1) Only diploid cells have a molecular clock mechanism which counts cell divisions prior to senescence. Two hypothetical examples of such mechanisms are described; however, the available evidence argues against a clock mechanism for aging in fibroblasts. 2) Cells become committed with a given probability to a slow buildup in protein errors, which leads after many divisions to a lethal error catastrophe. It can be shown that speeding up the rate at which the error catastrophe develops, as may occur in transformed cells, can convert a population of finite life-span to one with infinite growth. 3) The growth rate of diploid cells may not depend on the limiting concentration of any one protein. If so, cells with a low level of errors will not have a reduced generation time, and there will be no selection against them. On the other hand the uncontrolled growth of transformed cells may be reduced in rate by the presence of faulty proteins, so that there is continuous selection for those with the fewest errors. Finally, the analogous problem of the mortality of somatic cells and the immortality of the germ line is also briefly discussed.