Oller A R, Costa M, Oberdörster G
Nickel Producers Environmental Research Association, Durham, North Carolina 27713, USA.
Toxicol Appl Pharmacol. 1997 Mar;143(1):152-66. doi: 10.1006/taap.1996.8075.
The early epidemiological data indicated different carcinogenic risks from inhalation of different nickel compounds, but it was not clear what characteristics governed the intrinsic carcinogenic hazard of the various nickel compounds. Based on the earlier results, all soluble and insoluble nickel compounds were assumed to have the same carcinogenic mechanism albeit different potencies. Recent in vivo and in vitro studies challenged this assumption. In this paper an attempt is made to integrate the most relevant human, animal, and in vitro data into a general model that can help understand the different carcinogenic potentials of the various nickel compounds. In this perspective, it is recognized that there are two main components that could contribute to the development of lung cancer via exposure to certain nickel compounds. The first component corresponds to the heritable changes (genetic or epigenetic) derived from the direct or indirect actions of nickel compounds. The second component may be the promotion of cell proliferation elicited by certain nickel compounds. The different contributions of three nickel compounds to these two components are presented. This paper emphasizes the importance of recognizing the individuality of the different nickel species in reaching regulatory decisions and the fact that different risk assessment considerations may apply for compounds that appear to produce immortality and cancer by genetic/epigenetic mechanisms (like nickel subsulfide), compounds that may present a threshold for the induction of tumors in rats (like high-temperature nickel oxide), or compounds that may only have an enhancing effect on carcinogenicity (like nickel sulfate).
早期的流行病学数据表明，吸入不同的镍化合物会产生不同的致癌风险，但尚不清楚是哪些特性决定了各种镍化合物的内在致癌危害。基于早期的研究结果，所有可溶和不溶的镍化合物都被认为具有相同的致癌机制，尽管致癌效力不同。最近的体内和体外研究对这一假设提出了质疑。本文试图将最相关的人体、动物和体外数据整合到一个通用模型中，以帮助理解各种镍化合物不同的致癌潜力。从这个角度来看，人们认识到有两个主要因素可能通过接触某些镍化合物导致肺癌的发生。第一个因素对应于镍化合物直接或间接作用引起的可遗传变化（遗传或表观遗传）。第二个因素可能是某些镍化合物引发的细胞增殖促进作用。本文介绍了三种镍化合物对这两个因素的不同影响。本文强调了在做出监管决策时认识不同镍物种个体性的重要性，以及对于那些似乎通过遗传/表观遗传机制产生永生和癌症的化合物（如硫化亚镍）、在大鼠中可能存在肿瘤诱导阈值的化合物（如高温氧化镍）或可能仅对致癌性有增强作用的化合物（如硫酸镍）可能适用不同风险评估考量这一事实。
