Tokar Erik J, Benbrahim-Tallaa Lamia, Waalkes Michael P
Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Alexander Drive, Research Triangle Park, NC 27709, USA.
Met Ions Life Sci. 2011;8:375-401.
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.
在人类的整个进化过程中,金属一直存在于环境中,金属的使用是人类文明的关键。尽管如此,金属元素和化合物中包含一些剧毒物质,这些物质被人类广泛使用和/或在人类环境中广泛存在。这包括五种被认为是人类致癌物的金属制剂,即砷及砷化合物、铍及铍化合物、镉及镉化合物、六价铬化合物和镍化合物,所有这些在实验动物中也被证明是致癌物。人类大量接触这些致癌无机物,无论是通过职业接触、环境接触还是两者兼而有之。在工作场所,吸入是典型的接触途径,而从环境来源则会发生吸入或摄入。人类金属致癌物经常在进入部位引发肿瘤,吸入后肺癌是最常见的肿瘤。也会出现特定致癌物引发的肿瘤,比如砷暴露后引发的膀胱肿瘤,这是由于砷特有的生物动力学或机制所致。即使以最简单的元素形式存在,金属也并非惰性的,它们具有生物活性。然而,应该记住,这些无机致癌物以原子形式存在时,无法分解为毒性较小的亚单位,部分原因就在于此,它们作为环境人类致癌物才如此重要。本章重点关注已知的人类致癌金属制剂。