Spontaneous death of rat chloroleukaemia cells induced by an endogenous growth inhibitor

Abstract Objectives When rat chloroleukaemia ( CHL ) cells are grown undisturbed in a confined space, a genomic long interspersed nuclear element ( LINE ) is transcriptionally activated at a relatively low population density, followed by the retrotransposition of LINE and population death. This death programme is fundamentally different from conventional cell death pathways. Materials and methods This work is essentially based on the re‐analysis of relevant, old experimental data. Elemental analysis of a highly purified, long‐stored inhibitor sample was performed. Genomic sequence searches were performed using the basic local alignment search tool ( BLAST ). Results This death programme is initiated by an endogenous inhibitor secreted by CHL cells. The inhibitor is almost certainly identical to the pentapeptide pyroGlu‐Glu‐Asp‐Cys‐Lys, shown to be a cell line‐specific inhibitor of normal granulocytic cells. The inhibitor is derived from a highly conserved short open reading frame in mammalian genomes. Conclusions Although spontaneous population death may be a biological oddity restricted to rat CHL cells, we suggest that this death programme is responsible for the eradication of cancer cells following treatment with an inhibitor administered exogenously.