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.