From radioresistance to radiosensitivity: In vitro evolution of L5178Y lymphoma

To discuss the possible reasons for the loss of tumourigenicity and the acquisition of new phenotypic features (among them, sensitivity to X and UVC radiations) as a result of in vitro cultivation of L5178Y lymphoma cells.

Ten years ago the phenotypic differences between LY-R (original L5178Y maintained in vivo and examined in vitro) and LY-S lines were reviewed in detail by the author. The loss of tumourigenicity of LY-R cells upon in vitro cultivation accompanying the acquirement of the LY-S phenotype had been described earlier by Beer et al. (1983). In spite of their common origin, the sublines were shown to differ in their relative sensitivity to a number of DNA damaging agents and in numerous other features. Here, selected differences between LY-R and LY-S lines are briefly reviewed. It is proposed that Wallace's concept (2010a) that mitochondria are the interface between environmental conditions and the genome may explain the LY-R-LY-S conversion under prolonged in vitro cultivation.

The differences between the LY lines were probably of epigenetic rather than genetic character. The properties of LY-R cells changed as a result of exposure to an oxic in vitro milieu. The changes could be preconditioned by heteroplasmy and the selection of cells endowed with mitochondria best fitted to a high oxygen-low carbon dioxide environment.