From radioresistance to radiosensitivity: In vitro evolution of L5178Y lymphoma

Abstract

Purpose: 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.

Results: 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.

Conclusion: 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.

Keywords::

• L5178Y lymphoma
• LY sublines
• in vitro evolution
• radiosensitivity
• oxidative stress
• genomic instability
• mitochondrion
• epigenetics

Acknowledgements

I thank Dr Barbara Sochanowicz for critical remarks. The assistance of Monica Borrin-Flint in the preparation of the manuscript is gratefully acknowledged. The author is supported by the statutory grant of the Ministry of Science and Higher Education to the Institute of Nuclear Chemistry and Technology.

Declaration of interest

The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.