Waisberg Michael, Joseph Pius, Hale Beverley, Beyersmann Detmar
Department of Land Resource Science, University of Guelph, Guelph, Ont., Canada.
Toxicology. 2003 Nov 5;192(2-3):95-117. doi: 10.1016/s0300-483x(03)00305-6.
Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate.
镉是一种重金属，在工业中广泛使用，可通过职业暴露和环境暴露影响人体健康。在哺乳动物中，镉具有多种毒性作用，已被国际癌症研究机构列为人类致癌物。镉会影响细胞增殖、分化、凋亡及其他细胞活动。Cd2+ 不会催化芬顿型反应，因为它在生理条件下既不接受也不捐赠电子，且其遗传毒性较弱。因此，镉的致癌性涉及间接机制。在本综述中，将讨论多种机制，如基因表达和信号转导的调节、对细胞抗氧化系统酶的干扰及活性氧（ROS）的产生、DNA 修复和 DNA 甲基化的抑制、在细胞凋亡中的作用以及 E - 钙黏蛋白介导的细胞间黏附的破坏。镉会影响基因转录和翻译。目前已知的镉诱导基因的主要机制是通过增强蛋白质磷酸化以及激活转录和翻译因子来调节细胞信号转导途径。镉干扰抗氧化防御机制并刺激活性氧的产生，活性氧可能作为信号分子参与基因表达的诱导和细胞凋亡。镉对 DNA 修复过程的抑制是一种机制，通过该机制镉增强了其他物质的遗传毒性，并可能促成这种金属引发肿瘤。镉对 E - 钙黏蛋白介导的细胞间黏附的破坏可能进一步促进肿瘤的发展。很明显，虽然这些作用的相对权重难以估计，但存在多种机制促成了镉的致癌性。
