Discussion and Conclusions
Metals and metalloid elements are an essential feature of the human environment. Arsenic, beryllium, cadmium, chromium Cr(VI), cobalt, lead, nickel and thorium are identified as being carcinogenic in humans or animals but most are pro-carcinogens which become activated to advance cellular uptake and genotoxic or epigenetic action. Silica particles of respirable size are a cause of lung cancers but the carcinogenicity of indium and gallium semiconductor metals is unresolved. The human body can be exposed to at least 55 metal or metalloid elements in daily life or in industrial environments. At least arsenic, beryllium, cadmium, chromium, cobalt, lead, nickel, iron and microcrystalline silica are carcinogenic in humans. Mechanisms for carcinogenesis are complex and involve genotoxic/mutagenic effects and epigenetic factors. Radioactive isotopes emitting α-, β- or γ-particles are classified as carcinogens. Regulatory authorities have set out guidelines for diagnosis and classification of carcinogens and considerable weight is placed on results of epidemiological and human case studies, supported by experiments in laboratory animals. Classification of some elements is controversial and difficulties are experienced in classifications of nutrient ions such as iron and extrapolation of results of animal experiments. Iron, which is essential for oxygenation of the blood and many other functions, is potentially carcinogenic in overload conditions. It is acknowledged that chemical carcinogenesis is a multi-step process and that metals act as initiators and/or promoters of tumour formation. At least arsenic, lead, cadmium and Cr(VI) are complete carcinogens. All elements interact in the body in some way and emphasis is placed on the role of metal-binding proteins in modulating the intra- and extracellular functions of essential nutrients as well as in mitigating carcinogenic events.