Having developed the concept of chelation, but before attempting to discuss a relationship between metals and cancer, a short general review of the elements found in nature may be in order.

A number of so called bulk elements occur in nature in relatively high concentration; these are

C, H, O, N, S, P, Ca, K, Na, CI, Mg.

Iron can be considered in the bulk category for species containing hemoglobin. In addition to these atoms, an extraordinary array of elements are found in tissues in only trace amounts, many having no known biological function. The term trace elements is usually reserved for the few members of this group that do have known biochemical activity, but this is an unfortunate use, giving rise to wrong impressions. Some authors prefer the terms minor elements or micro elements, but whatever the suggested alternative, none has received wide usage as yet.

Reported to be present in tissues at varying concentrations are these elements listed in order of atomic number:

Li, B, F, Al, Si, Ti, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Br, Rb, Sr, Mo, Sn, I, Ba, Pb.

Added to this may be V, Ag, Au. Of all these elements only a few have been definitely associated with enzyme activity: Ca, Mg, Mn, Fe, Cu, Zn, Mo; Co is an integral part of vitamin B12. In plants,

Fe, Cu, Mn, Zn, B, Sc and Mo may be required. Cobalt and iodine, though also present, have no known function. This is true also of other elements that occur in larger than trace amounts.

Lower forms of life may have unusual metal requirements, as molybdenum in nitrogen fixing bacteria, gallium in Aspergillus niger, vanadium in protochordates and lead in gonococcus. As time goes on, new biological functions are being found for elements that have heretofore not been considered "essential." Thus, roles have been assigned recently for cadmium and selenium. New metal complexes of biological materials are frequently described, such as the recent report of uranyl protoporphyrin.

Of interest here is that with the exception of magnesium, all the trace metals associated with enzymes (like copper in uricase, zinc in carbonic anhydrase, and iron in catalase) are found in the periodic chart as transition elements, and are characterized by their ease of forming complex ions or chelates with appropriate organic molecules. Also, it should be recognized that a combination of metals may be necessary for enzymatic function, i.e., magnesium and manganese in phosphorylase, and iron and molybdenum for xanthine oxidase in a ratio of 8:1:4. Metals, therefore, do interact in biological systems. Massive intake of one trace element will influence the absorption of others; molybdenum will affect copper retention; a deficiency of copper will limit the requirement for iron; copper may counteract zinc or molybdenum toxicity. There is also the phenomenon of competition of one element with another for a site in a specific biological tissue. Both strontium and beryllium have an affinity for bone and can cause rickets, whereas all group VII elements of the periodic chart go to the thyroid gland.

Appendix

Those elements reported carcinogenic in at least one species, regardless of method of tumor induction, are shown with an "a," meaning active.

Periodic Table Of The Elements