Possible Mechanisms of Mercury Toxicity and Cancer Promotion: Involvement of Gap Junction Intercellular Communications and Inflammatory Cytokines

Figure 2

Proposed role of mercury as epigenetic/promoter carcinogen. The progressive multistep transformation of a normal cell to a cancer cell is shown schematically. The indicated phases (i.e., initiation → latency → promotion → progression) are those commonly accepted for cancer development. Mercury (Hg(II)) is indicated to act in the promotion phase by causing an unbalance in the reactive oxygen species (ROS) homeostasis accomplished by selective inhibition of selenocysteine antioxidant enzymes. Mitochondria are also shown as a major ROS generator. The Hg(II)-induced prooxidative state in turn would result in inhibition of the gap junction intercellular communication (GJIC) and of the proinflammatory cytokine release. Both mechanisms might on one hand isolate cells from tissue-specific homeostasis promoting their proliferation and on the other hand tamper the immune system defense/surveillance checkmating the whole organism. The Cx43-related open gap junction is shown as progressively closing in the transitions following the “latent” state.