The Role of Combined Metal Interactions in Metal Carcinogenesis: A Review

Abstract

Exposures to complex mixtures of metals in the workplace or environment are more likely to occur than exposures to a single metal alone. The evidence shows that exposures to complex metal mixtures can enhance the risk of cancer in certain human populations. The findings of several studies have suggested, however, that certain metal-metal interactions can inhibit carcinogenic activity. The mechanisms of metalmetal interactions in human carcinogenesis are relatively unknown. Metals represent a highly diverse group of agents: each metal can act through different mechanisms and in one or more steps of the carcinogenic process. Some potential mechanisms may involve direct reactions of the metal with DNA or indirect mechanisms that include modification of DNA repair, DNA methylation status, and metabolic processes involved in DNA replication and expression. Lipid peroxidation and the generation of free radicals induced by certain metals can affect DNA integrity. This review will address the role of metals in carcinogenesis and how concomitant exposure to metal mixtures can influence cancer induction. The most current mechanistic data regarding metal interactions and its implications in human carcinogenesis will be discussed. Furthermore, research gaps will be identified to provide data that will improve risk assessments for complex metal mixtures encountered in the workplace and environment.

Distribution and Genotoxic Effects After Successive Exposure to Different Uranium Oxide Particles Inhaled by Rats

“…At the same time, the study of UO 4 bioaccumulation showed that the UO 4 biokinetics in the kidneys, gastrointestinal tract, and excreta, but not in the lungs, were slightly modified by previous UO 2 exposures. All these results show that both genotoxic and biokinetics effects of uranium may depend on preexposure and that repeated exposure induces a potentiation effect compared with acute exposure.Exposures to complex mixtures of metals in the workplace are more likely to occur than exposures to a single compound alone (Madden, 2003). Various forms of uranium (U) are found in the nuclear industry with a variety of isotopic compositions…”

“…Exposures to complex mixtures of metals in the workplace are more likely to occur than exposures to a single compound alone (Madden, 2003). Various forms of uranium (U) are found in the nuclear industry with a variety of isotopic compositions…”

“…A previous study showed that exposure to depleted insoluble U by inhalation resulted in DNA strand breaks in different cell types with an effect of potentiation after repeated inhalations (Monleau et al, 2006b). However, in the event of exposure by inhalation to various U compounds, the combined effects are unknown even though exposure to metal mixtures can lead to synergistic or antagonistic effects (Madden, 2003). Indeed, exposure to one compound or to mixtures induced different genotoxic, apoptotic, and inflammatory responses, suggesting the possibility of combined effects (De Boeck et al, 1998Lombaert et al, 2004;Miller et al, 2004).…”

The Influence of Arsenic, Lead, and Mercury on the Development of Cardiovascular Diseases

“…Exposures to complex metal mixtures can enhance the risk of cancer in certain human populations. e �ndings of the review show that combined metal interactions are more important than the sum of the individual metal effects [131]. Combined with mercury or cadmium no observed effect Level (NOEL) dose of lead showed toxicity, indicating that exposure limits may be inefficient in combined exposure situations [132].…”

Role of Oxidative Stress in Transformation Induced by Metal Mixture

“…Among these proposed mechanisms, oxidative stress is commonly observed in in vivo and in vitro systems during exposure to these metals as mixture [4]. However, several studies suggest that certain metal-metal interactions inhibit carcinogenic activity [14]. Because humans are continually exposed to complex metal mixtures at low doses, it is necessary to determine the mechanism underlying the transformation process.…”