Mercury and human genotoxicity: critical considerations and possible molecular mechanisms

Mercury compounds versatility explains their numerous applications in diverse areas of industry. The growing use of this metal has resulted in a significant increase of environment contamination and episodes of human intoxication, arousing the concern of international organisms. Meanwhile, consequences of these intoxication outbreaks are still not fully understood, especially if we consider long-term effects of chronic exposure to relatively low levels of mercury compounds. In the present manuscript, studies about the genotoxicity of mercury compounds, performed in vitro, in vivo, and/or including epidemiologic studies of human populations were reviewed. Some mercury compounds are known as teratogenic agents, especially affecting the normal development of the central nervous system; however, the connection between mercury exposure and carcinogenesis remains controversial. Since 1990s, epidemiological studies have begun to include an increasing number of human subjects, making the results more reliable: thus, increased genotoxicity was demonstrated in human populations exposed to mercury through diet, occupation or by carrying dental fillings. In fact, concentrations of methylmercury causing significant genotoxic alterations in vitro below both safety limit and concentration were associated with delayed psychomotor development with minimal signs of methylmercury poisoning. Based on mercury's known ability to bind sulfhydryl groups, several hypotheses were raised about potential molecular mechanisms for the metal genotoxicity. Mercury may be involved in four main processes that lead to genotoxicity: generation of free radicals and oxidative stress, action on microtubules, influence on DNA repair mechanisms and direct interaction with DNA molecules. All data reviewed here contributed to a better knowledge of the widespread concern about the safety limits of mercury exposure.