Suicidal death of rat chloroleukaemia cells by activation of the long interspersed repetitive DNA element (L1Rn).

Abstract

Rat chloroleukaemia cells, maintained in suspension culture in different media, show rapid exponential growth without cell loss. At about half of the maximal population density the long interspersed repetitive DNA element (L1Rn) is suddenly transcriptionally activated without any obvious exogenous reason. Population growth is then inhibited and, within about 24 h after reaching the maximal density, the population undergoes programmed death (apoptosis). Suicidal cell death is caused by sudden incorporation, apparently by retroposition via an RNA intermediate, of about 300,000 copies of the L1Rn element into random locations in the cell genome, thus creating lethal mutations. The preceding growth inhibition is associated with repression, to an undetectable level, of c-Ki-ras expression. Up to the point of massive L1Rn incorporation and cell death, all phenomena are quickly reversible by subculturing; medium change alone is not sufficient. Biological implications of these surprising findings are discussed.