14:Metal Ions in Human Cancer Development

Metals have been in the environment during the entire evolution of man and the use of metals is key to human civilization. None-the-less, several very toxic species are included in the metallic elements and compounds either widely used by man and/or widely found in the human environment. This includes the five metallic agents considered human carcinogens, namely arsenic and arsenic compounds, beryllium and beryllium compounds, cadmium and cadmium compounds, chromium(VI) compounds, and nickel compounds, all of which are proven carcinogens in laboratory animals as well. There is significant human exposure to these carcinogenic inorganics, either occupationally, through the environment, or both. Inhalation is typical in the workplace while inhalation or ingestion occurs from environmental sources. Human metallic carcinogens frequently cause tumors at the portal of entry and lung cancers are the most common tumor after inhalation. Agent-specific tumors occur as well, like urinary bladder tumors after arsenic exposure, which are due to biokinetics or mechanisms that are specific to arsenic. Even in their simplest elemental form, metals are not inert, and they have biological activity. However, it should be kept in mind that these inorganic carcinogens, when in the atomic form, cannot be broken down into less toxic subunits, and this, in part, is why they are so important as environmental human carcinogens. This chapter focuses on the metallic agents that are known human carcinogens.