Chromium (VI) Induces a Telomerase-Dependant Bystander Effect to Cause Genomic Instability in Human Cells
Funding source: Technological Sector Research Strand I
Personnel: N Cogan, FM Lyng, CP Case
There is current interest in the role of the bystander effect in chromosomal and genomic instability. The bystander effect has so far been shown to occur following exposure to ionizing radiation. Cells directly exposed to radiation induce genomic instability in neighbouring ‘bystander’ cells either through secretion of factors into the growth medium or through transfer of a signal via gap junctions. A previous study demonstrated that short term (24 hour) exposures to chromium and vanadium lead to an increase in genomic instability up to 30 days after exposure. The ectopic expression of hTERT protects against this instability. In the current study, we have addressed whether, like radiation, metals are able to induce a bystander effect that would cause chromosomal instability. To do this we treated BJ human fibroblast cells for 24 hours with 0.4 M potassium dichromate (K2Cr2O7). The cells were washed 5 times to remove any trace of metal ions and incubated in fresh growth medium for 1 hour. This medium was filtered and transferred to non metal-exposed BJ cells for 24 hours. Our results show that there was an increase in micronuclei, nucleoplasmic bridges and H2AX foci in cells subjected to a medium transfer bystander treatment. We also demonstrated that ectopic expression of hTERT protects cells from the bystander response. In conclusion, we demonstrate for the first time, a metal-induced bystander effect that is attenuated in the presence of telomerase.
