There is currently a great interest in delayed chromosomal and other damaging effects of low-dose exposure to a variety of
pollutants which appear collectively to act through induction of stress-response pathways related to oxidative stress and ageing. These have been studied mostly in the radiation field but evidence is accumulating that the mechanisms can also be triggered by chemicals, especially
heavy metals. Humans are exposed to metals, including
chromium (
Cr) (VI) and
vanadium (V) (V), from the environment, industry and surgical implants. Thus, the impact of low-dose stress responses may be larger than expected from individual toxicity projections. In this study, a short (24 h) exposure of human fibroblasts to low doses of
Cr (VI) and V (V) caused both acute chromosome damage and
genomic instability in the progeny of exposed cells for at least 30 days after exposure. Acutely,
Cr (VI) caused chromatid breaks without
aneuploidy while V (V) caused
aneuploidy without chromatid breaks. The longer-term
genomic instability was similar but depended on hTERT positivity. In
telomerase-negative hTERT- cells,
Cr (VI) and V (V) caused a long lasting and transmissible induction of dicentric chromosomes, nucleoplasmic bridges, micronuclei and
aneuploidy. There was also a long term and transmissible reduction of clonogenic survival, with an increased
beta-galactosidase staining and apoptosis. This instability was not present in
telomerase-positive hTERT+ cells. In contrast, in hTERT+ cells the metals caused a persistent induction of
tetraploidy, which was not noted in hTERT- cells. The growth and survival of both
metal-exposed hTERT+ and hTERT- cells differed if they were cultured at subconfluent levels or plated out as colonies.
Genomic instability is considered to be a driving force towards
cancer. This study suggests that the type of
genomic instability in human cells may depend critically on whether they are
telomerase-positive or -negative and that their sensitivities to metals could depend on whether they are clustered or diffuse.