Crespo-López Maria Elena, Macêdo Gisele L, Pereira Susana I D, Arrifano Gabriela P F, Picanço-Diniz Domingos L W, do Nascimento José Luiz M, Herculano Anderson M
Laboratório de Farmacologia Molecular, Instituto de Ciencias Biologicas, Universidade Federal do Para (UFPA), 66075-110 Belem-PA, Brazil.
Pharmacol Res. 2009 Oct;60(4):212-20. doi: 10.1016/j.phrs.2009.02.011. Epub 2009 Mar 9.
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.
汞化合物的多功能性解释了它们在不同工业领域的众多应用。这种金属使用的增加导致了环境污染的显著增加和人类中毒事件的发生，引起了国际组织的关注。与此同时，这些中毒事件的后果仍未得到充分理解，特别是当我们考虑长期接触相对低水平汞化合物的影响时。在本手稿中，对在体外、体内进行的关于汞化合物遗传毒性的研究，以及/或者包括对人群的流行病学研究进行了综述。一些汞化合物被认为是致畸剂，尤其会影响中枢神经系统的正常发育；然而，汞暴露与致癌作用之间的联系仍然存在争议。自20世纪90年代以来，流行病学研究开始纳入越来越多的人类受试者，使得结果更加可靠：因此，在通过饮食、职业或补牙接触汞的人群中证实了遗传毒性增加。事实上，在体外低于安全限值和浓度的情况下，导致显著遗传毒性改变的甲基汞浓度与精神运动发育迟缓以及甲基汞中毒的最小迹象有关。基于汞已知的结合巯基的能力，人们提出了关于该金属遗传毒性潜在分子机制的几种假说。汞可能参与导致遗传毒性的四个主要过程：自由基的产生和氧化应激、对微管的作用、对DNA修复机制的影响以及与DNA分子的直接相互作用。这里综述的所有数据有助于更好地了解人们对汞暴露安全限值的广泛关注。
