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

Abstract EN

A number of observations indicate that heavy metals are able to alter cellular metabolic pathways through induction of a prooxidative state.

Nevertheless, the outcome of heavy metal-mediated effects in the development of human diseases is debated and needs further insights.

Cancer is a well-established DNA mutation-linked disease; however, epigenetic events are perhaps more important and harmful than genetic alterations.

Unfortunately, we do not have reliable screening methods to assess/validate the epigenetic (promoter) effects of a physical or a chemical agent.

We propose a mechanism of action whereby mercury acts as a possible promoter carcinogen.

In the present contribution, we resume our previous studies on mercury tested at concentrations comparable with its occurrence as environmental pollutant.

It is shown that Hg(II) elicits a prooxidative state in keratinocytes linked to inhibition of gap junction-mediated intercellular communication and proinflammatory cytokine production.

These combined effects may 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.

Since Hg(II) is not a mutagenic/genotoxic compound directly affecting gene expression, in a broader sense, mercury might be an example of an epigenetic tumor promoter or, further expanding this concept, a “metagenetic” effector.