DNA damaging bystander signalling from stem cells, cancer cells and fibroblasts after Cr(VI) exposure and its dependence on telomerase.
The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells. Here we show that a low and short dose of Cr(VI) can induce stem cells, cancer cells and fibroblasts to chronically secrete bystander signals, which cause DNA damage in neighboring cells. The Cr(VI) induced bystander signaling depended on the telomerase status of either cell. Telomerase negative fibroblasts were able to receive DNA damaging signals from telomerase positive or negative fibroblasts or telomerase positive cancer cells. However telomerase positive fibroblasts were resistant to signals from Cr(VI) exposed telomerase positive fibroblasts or cancer cells. Human embryonic stem cells, with positive Oct4 staining as a marker of pluripotency, showed no significant increase of DNA damage from adjacent Cr and mitomycin C exposed fibroblasts whilst those cells that were negatively stained did. This selectivity of DNA damaging bystander signaling could be an important consideration in developing therapies against cancer and in the safety and effectiveness of tissue engineering and transplantation using stem cells.
Bristol Implant Research Centre, University of Bristol, Bristol, UK.
Nicola
N
Cogan
Duncan M
DM
Baird
Ryan
R
Phillips
Lucy A
LA
Crompton
Maeve A
MA
Caldwell
Miguel A
MA
Rubio
Roger
R
Newson
Fiona
F
Lyng
C Patrick
CP
Case
D001205:Ascorbic Acid / Q000494:pharmacology; D024201:Bystander Effect / Q000502:physiology*; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity*; D004249:DNA Damage; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006657:Histones / Q000378:metabolism; D006801:Humans; D015162:Micronucleus Tests; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C468783:H2AX protein, human; D006657:Histones; D014409:Tumor Necrosis Factor-alpha; D002857:Chromium; C074702:chromium hexavalent ion; C509186:TERT protein, human; D019098:Telomerase; D001205:Ascorbic Acid