Differential effect of the duration of exposure on the carcinogenicity of cadmium in MCF10A mammary epithelial cells.

The carcinogenic role of cadmium (Cd ²⁺ ) in breast cancer is still debatable. Current data points to duration of exposure as the most important element. In our study, we designed an in vitro model to investigate the effects of 3 weeks versus 6 weeks of low-level CdCl ₂ exposure on MCF10A cells. Our results demonstrated that after 3 weeks of CdCl ₂ exposure the cells displayed significant changes in the DNA integrity, but there was no development of malignant features. Interestingly, after 6 weeks of exposure, the cells significantly increased their invasion, migration and colony formation capacities. Additionally, MCF10A cells exposed for 6 weeks to CdCl ₂ had many dysregulated genes (4905 up-regulated and 4262 down-regulated). As follows, Cd-induced phenotypical changes are accompanied by a profound modification of the transcriptomic landscape. Furthermore, the molecular alterations driving carcinogenesis in MCF10A cells exposed to CdCl ₂ were found to be influenced by the duration of exposure, as in the case of MEG8. This long non-coding RNA was down-regulated at 3 weeks, but up-regulated at 6 weeks of exposure. In conclusion, even very low levels of Cd (0.5 μM) can have significant carcinogenic effects on breast cells in the case of subchronic exposure.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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