title: Medium from irradiated cells induces dose-dependent mitochondrial changes and BCL2 responses in unirradiated human keratinocytes.
abstract: Exposure of unirradiated human keratinocytes to irradiated cell conditioned medium (ICCM) is known to cause a cascade of events that leads to reproductive death and apoptosis. This study investigates the effect of ICCM on clonogenic survival, mitochondrial mass and BCL2 expression in unirradiated keratinocytes. Exposure to 5 mGy, 0.5 Gy and 5 Gy ICCM resulted in a significant decrease in clonogenic survival. Human keratinocytes incubated with ICCM containing an antioxidant, N-acetylcysteine, showed no significant decrease in clonogenic survival. HPV-G cells incubated with ICCM containing a caspase 9 inhibitor showed no significant decrease in clonogenic survival when the ICCM dose was < or =0.5 Gy. A significant increase in mitochondrial mass per cell was observed after exposure to 5 mGy and 0.5 Gy ICCM. A change in the distribution of the mitochondria from a diffuse cytoplasmic distribution to a more densely concentrated perinuclear distribution was also observed at these doses. No significant increase in mitochondrial mass or change in distribution of the mitochondria was found for 5 Gy ICCM. Low BCL2 expression was observed in HPV-G cells exposed to 5 mGy or 0.5 Gy ICCM, whereas a large significant increase in BCL2 expression was observed in cells exposed to 5 Gy ICCM. This study has shown that low-dose irradiation can cause cells to produce medium-borne signals that can cause mitochondrial changes and the induction of BCL2 expression in unirradiated HPV-G cells. The dose dependence of the mitochondrial changes and BCL2 expression suggests that the mechanisms may be aimed at control of response to radiation at the population level through signaling pathways.
authors.affiliation: Radiation and Environmental Science Centre, Dublin Institute of Technology, Dublin, Ireland. pelcg_30@yahoo.com
authors.forename: Paula
authors.initials: P
authors.lastname: Maguire
authors.forename: Carmel
authors.initials: C
authors.lastname: Mothersill
authors.forename: Colin
authors.initials: C
authors.lastname: Seymour
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Lyng
mesh_terms: D024201:Bystander Effect / Q000502:physiology* / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects* / Q000648:ultrastructure; D008928:Mitochondria / Q000528:radiation effects* / Q000648:ultrastructure*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011829:Radiation Dosage
chemical_list: D017077:Culture Media, Conditioned; D019253:Proto-Oncogene Proteins c-bcl-2