Waalkes M P, Coogan T P, Barter R A
Inorganic Carcinogenesis Section, Frederick Cancer Research and Development Center, National Cancer Institute, MD 21702-1201.
Crit Rev Toxicol. 1992;22(3-4):175-201. doi: 10.3109/10408449209145323.
Metals are an important and emerging class of carcinogens. At least three metals, specifically nickel, chromium, and arsenic, are confirmed human carcinogens, and several more are suspected to have carcinogenic potential in man. Considering that the list of known human carcinogens of any type is very small, it becomes clear that metals make up a substantial portion of the list. Furthermore, many metals are very potent carcinogens in laboratory animals. Despite this, relatively little attention has been given to the topic of metal carcinogenesis. The reasons for this relative lack of attention are not clear but perhaps are fostered by a perception that, because metals are the simplest of molecules, their mechanism of action must also be simple. This could not be farther from the truth and, although no clear mechanisms have emerged in the area of metal carcinogenesis, it has become apparent that they are anything but simple. Metal carcinogens possess several unique characteristics including a remarkable target site specificity. Detection of the mechanism, or mechanisms, of metal carcinogenesis has, however, proven elusive, in part because of a wide diversity of metallic carcinogenic agents and the intricate nature of metal interactions in biologic systems. The following review explores this broad topic, with special emphasis on toxicological principles including dose-response relationships and potential mechanisms, using cadmium as an example.
金属是一类重要且正在兴起的致癌物。至少有三种金属，即镍、铬和砷，已被确认为人类致癌物，还有几种金属被怀疑对人类具有致癌潜力。鉴于已知的任何类型的人类致癌物清单都非常短，很明显金属在该清单中占了相当大的比例。此外，许多金属在实验动物中是非常强效的致癌物。尽管如此，金属致癌作用这一主题相对而言却很少受到关注。这种相对缺乏关注的原因尚不清楚，但可能是由于一种观念，即认为金属是最简单的分子，其作用机制也必然简单。但事实远非如此，尽管在金属致癌作用领域尚未出现明确的机制，但很明显它们绝非简单。金属致癌物具有几个独特的特征，包括显著的靶位点特异性。然而，事实证明，检测金属致癌作用的一种或多种机制很困难，部分原因是金属致癌剂种类繁多，以及生物系统中金属相互作用的复杂性。以下综述探讨了这个广泛的主题，特别强调了毒理学原理，包括剂量反应关系和潜在机制，并以镉为例进行说明。
