Bystander effect induced changes in apoptosis related proteins and terminal differentiation in in vitro murine...

Radiation-induced bystander effects are now an established phenomenon seen in numerous cell and tissue culture models. The aim of this investigation was to examine the bystander signal and response in a multicellular primary tissue culture system in vitro.

Murine bladder samples were explanted and directly exposed to gamma radiation, or treated with irradiated tissue conditioned medium (ITCM) generated from the directly irradiated cultures.

Results indicated that there was a strong bystander signal produced by the tissue that caused both dose-dependent and -independent changes in the ITCM treated tissue. Significantly increased B-cell lymphoma 2 (Bcl2) expression was noted after treatment with 0.5Gy and 5Gy ITCM (approximately 80%), while dose-dependent changes were observed in c-myelocytomatosis (cMyc) (39.48% at 0.5 Gy ITCM, 81.28% at 5 Gy ITCM) and the terminal differentiation marker uroplakin III (17.88% at 0.5 Gy). Nuclear fragmentation was also significantly increased at both doses of ITCM.

These data suggest that the bystander signal produced in a multicellular environment induces complex changes in the ITCM-treated culture, and that these changes are reflective of a coordinated response to maintain integrity throughout the tissue.