Level of ribosomal RNA required for stimulation from quiescence increases during cellular aging in vitro of mammalian fibroblasts.

We have investigated the relation between cell size in terms of cellular ribosomal RNA (rRNA) content and proliferation of diploid human and rat embryo fibroblasts during their aging in vitro. During phase III of the proliferative lifespan in vitro, cellular rRNA content increases by a factor of nearly 3. For very different regimes of stimulation of quiescent cells, a strict correlation was observed, between the proportion of cells stimulated and cellular rRNA content, resembling a steep threshold curve. During aging in vitro, these characteristic curves exhibit an essentially parallel shift to higher values of cellular rRNA content (to higher 'thresholds'). Upon establishment as a permanent cell line, the relation between proliferation stimulation and cellular rRNA ceases to change with further subculturing. It is suggested that the essence of transformation of fibroblasts with a myc-type of oncogenes is a reduction and stabilizing of the critical rRNA content required for proliferation.