Metal-induced carcinogenesis, oxidative stress and hypoxia signalling.

Heavy metal-induced carcinogenesis is well documented by epidemiological studies. Several diverse mechanisms of cancer induction may be involved, depending on the form of every metal and the tissue that is exposed. Over the recent years, induction of signalling pathways that regulate key cellular responses related to cancer growth and progression by metals has been the focus of many studies. The unravelling of these pathways and the deciphering of their interplay with metals should allow a better understanding of metal toxicity and hopefully will enable development of prophylactic strategies and therapeutic approaches. In this work, we review the mechanisms of carcinogenesis caused by heavy metals emphasizing on the involvement of the hypoxia signalling pathway by metal-induced generation of reactive oxygen species and oxidative stress generation in cancer progression.