Metal Carcinogenesis

Metals can be carcinogenic if their local cellular concentration becomes sufficiently high so that they can compete with the normal metals for the available binding site in the lattice and thus aid in the synthesis of abnormal polymeric nucleic acids. Thus cancers of different tissues should be in the main different, for each tissue concentrates different metals.

Chemical Carcinogenesis

A carcinogen may, as a chelating agent, complex with an abnormal metal and form a chelate. All carcinogenic agents have favorable partition coefficients. This complex carrying the metal may penetrate the cell wall. Once within the cell, the chelate may partially dissociate and liberate a source of abnormal metals for modifying enzyme activity or nucleic acid formation. At the same time the carcinogenic chelating agent becomes available to compete with the enzyme for the essential trace element. If two exogenous agents compete for the trace element or abnormal metal, the probability of this abnormal metal's being used by the enzyme or nucleic acid becomes less. Thus, in other words, one carcinogen may interfere with the carcinogenic properties of another.

Carcinogenic chelating agents once in the cell could also conceivably compete with the nucleic acid units for the normal metals available, thus allowing a lower concentration of the abnormal metals to be effective.

The carcinogenic hydrocarbons may be complexed to nucleic acids via transition element ions. The purine-pyrimidine pairs from different chains form a phenanthrene-like unit. The poly-nuclear hydrocarbons must also have a phenanthrene nucleus to be carcinogenic; linear rings do not have this shape. The nucleic acids may enfold the carcinogenic hydrocarbon and thus form new groupings or have a different conformation. New DNA units give rise to new RNA, which in turn act as a template for new proteins.

Bivalent cations Ca++ and Mg++ are associated with intracellular transphosphorylation. Ca++ accelerates the transformation of ATP to ADP, as does Mg++. If either cation is removed by chelation, new chromosomal aberrations may appear. Neoplastic growth, may, therefore, affect some aspect of Ca++ regulation.