AUTHOR=Fischietti Mariafausta , Fratini Emiliano , Verzella Daniela , Vecchiotti Davide , Capece Daria , Di Francesco Barbara , Esposito Giuseppe , Balata Marco , Ioannuci Luca , Sykes Pamela , Satta Luigi , Zazzeroni Francesca , Tessitore Alessandra , Tabocchini Maria Antonella , Alesse Edoardo 

TITLE=Low Radiation Environment Switches the Overgrowth-Induced Cell Apoptosis Toward Autophagy

JOURNAL=Frontiers in Public Health

VOLUME=Volume 8 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2020.594789

DOI=10.3389/fpubh.2020.594789

ISSN=2296-2565

ABSTRACT=Low radiation doses can affect and modulate cell responses to various stress stimuli, resulting in perturbations leading to resistance or sensitivity to damage. To investigate mechanisms taking place at environmental radiation exposure, we set-up twin biological models, one growing in a low radiation environment (LRE) laboratory, at the Gran Sasso National Laboratory, and one growing in a reference radiation environment (RRE) laboratory, at the Italian National Health Institute (Istituto Superiore di Sanità, ISS). 
Studies were performed on pKZ1 A11 mouse hybridoma cells, which derived from the pKZ1 transgenic mouse model used to study the effects of low dose radiation, and focused on the analysis of cellular/molecular end-points, such as proliferation and expression of key proteins involved in stress response, apoptosis and autophagy.
Cells cultured up to 4 weeks in LRE showed no significant differences in proliferation rate compared to cell cultured in RRE. However, PARP1 cleavage and caspase-3 activation were strongly observed in over-growing cells in RRE, indicating a triggering of apoptosis due to growth-stress conditions. Notably, in LRE conditions, cells responded to overgrowth stress by switching toward autophagy. Interestingly, autophagic signaling induced by overgrowth in LRE correlated with activation of p53. 
Finally, the gamma component of environmental radiation did not significantly influence these biological responses, since cells grown at LRE either in incubators with or without an iron shield did not modify their responses. 
Overall, in vitro data presented here corroborate the hypothesis that environmental radiation contributes to the development and maintenance of balance and defense mechanisms in organisms.