Heavy metal and cancer

Atomic absorption spectroscopy (AAS) has been used to reveal an appreciable difference in the pattern of metal ions distributed throughout the blood plasma of cancer patients compared with control volunteers.

Blood is a widely used biological sample in trace metal research, partly because it is so easy to obtain samples but moreover because it is the medium by which toxic and non-toxic trace metal ions are transported through the body. A study of trace metals in blood can, therefore, provide direct evidence of their metabolism. Chemist Munir Shah of the Quaid-i-Azam University, in Islamabad, Pakistan, working with biochemists Qaisara Pasha and Salman Malik have focused on these qualities in an investigation of plasma trace metal concentrations in cancer patients with perhaps surprising results.

"The role of different trace metals in the normal vital activities and initiation of some diseased has long been known," the researchers point out, "however, until recently clinical recognition was limited to very few of the trace metals." It is now assumed that almost all the chemical elements have some involvement whether positive or detrimental in a wide range of physiological processes to varying degrees. "Moreover," the team adds, "any changes in the environment as well as in the human body itself can trigger changes in trace metal composition of any organ or tissue." The consequences of such change might be linked to the emergence of a disease state.

One such disease state in which trace metal levels could play a role is cancer. Until recently, cancer has been considered a purely genetic disease, or rather group of diseases. In which some agent, whether endogenous or exogenous, initiates runaway cell replication or otherwise disrupts the normal process of cell death, leading to the growth of a tumour or the spread of cancerous cells through the lymph system or blood.

Shah points out that, diet has become an increasingly well-recognized factor in cancer incidence, and he suggests that it may be possible to glean significant insights into cancer from an analysis of food consumption patterns. Many studies suggest that rather than being a simple problem of gene damage, cancer is a disease with multiple interwoven causes. As such, the researchers say, "the role of trace metals in the development and inhibition of cancer has a complex character and raises many questions."

Previous researchers have tried to uncover a relationship between the presence of trace metals in the body and the development of human cancers. Given that so many trace metals underpin the functions of a huge range of enzymes and proteins involved in cell signalling, lifecycles, replication, and cell death, it would be odd if trace metals did not have a key role to play in cancer.

Of course, metals such as cadmium, are known to be mammalian mutagens, damaging DNA, and high levels have been linked to prostate, renal and lung cancers. Similarly, the researchers add, raised concentrations of lead have been associated with stomach, small intestine, large intestine, ovary, renal, lung, myeloma, and leukaemia.

Other metals, including chromium and zinc have been observed to speed up tumour growth in animal models. In humans, these metals have been associated with the more rapid progression of breast, colon, rectum, ovary, lung, pancreas, bladder cancers, and leukaemia. Shah and colleagues also point out that nickel too is a mutagen and has been linked to lung and nasal cancer as are antimony and cobalt.

There are several trace metals that are essential to life. Iron and copper, for instance, play a crucial role in various metabolic processes. However, there is some evidence of the carcinogenicity of iron and significantly raised plasma levels of copper have also been associated with malignancy. The link perhaps being that these metals can trigger hydroxyl radical formation with attendant DNA damage.

The team has used flame AAS and a multivariate principal component analysis to estimate the comparative distribution of trace metals in the plasma of cancer patients and healthy volunteers. They analysed aluminium, antimony, cadmium, calcium, cobalt, chromium, copper, iron, lead, lithium, magnesium, manganese, molybdenum, nickel, potassium, sodium, strontium, and zinc.

They found that in the plasma of cancer patients the mean concentrations of the essential metals (Ca, Fe, K, Mg, Na, and Zn) were significantly lower in the healthy volunteers. Similarly, the average concentrations of Cd, Cr, Cu, Mn, Mo, Ni, Pb, Sb, and Sr were much higher in the cancer patients. The analysis revealed several close correlations between specific pairs of metals in the cancer patients: Fe-Mn, Ca-Mn, Ca-Ni, Ca-Co, Cd-Pb, Co-Ni, Mn-Ni, Mn-Zn, Cr-Li, Ca-Zn and Fe-Ni, whereas this coupling pattern was very different in the controls.

"The study indicates appreciably different patterns of metal distribution and mutual relationships in the plasma of cancer patients in comparison with controls," the researchers conclude. Further studies are now needed to determine how and why such marked changes in trace metal concentrations are observed in cancer patients. Metabolism in cancer patients is obviously changed significantly by specific trace metals but whether that is a cause or an effect remains to be seen.