Mechanisms in cadmium-induced carcinogenicity: recent insights
Mechanisms in cadmium-induced carcinogenicity: recent insights
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DOI：
10.1007/s10534-010-9330-4
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发表时间：
2010-10-01
期刊：
影响因子：
3.5
通讯作者：
Hartwig, Andrea
中科院分区：
文献类型：
--
作者：
Hartwig, Andrea
镉是一种环境污染物，在工作场所和一般人群中存在相关暴露。致癌性早已确立，对肺和肾肿瘤最明显，但对其他肿瘤部位也有越来越多的证据。虽然与DNA的直接相互作用似乎不太重要，但在不同的实验系统中已经证明了对DNA损伤的细胞反应的干扰、细胞生长的失调以及对凋亡的抵抗。关于DNA修复过程，镉已被证明干扰核苷酸切除修复，碱基切除修复和错配修复;后果是增加对其他DNA损伤剂和内源性诱变剂的易感性。此外，镉诱导细胞增殖，使负性生长刺激物（如肿瘤抑制蛋白p53）失活，并引起对凋亡的抗性。特别是这些多种机制的组合可能会导致镉适应细胞中高度的基因组不稳定性，不仅与肿瘤的发生有关，而且与肿瘤发展的后期步骤有关。未来的研究需要澄清这些相互作用对人类低暴露条件的相关性。
Cadmium is an environmental pollutant, with relevant exposures at workplaces and in the general population. The carcinogenicity has been long established, most evident for tumors in the lung and kidney, but with increasing evidence also for other tumor locations. While direct interactions with DNA appear to be of minor importance, the interference with the cellular response to DNA damage, the deregulation of cell growth as well as resistance to apoptosis have been demonstrated in diverse experimental systems. With respect to DNA repair processes, cadmium has been shown to disturb nucleotide excision repair, base excision repair and mismatch repair; consequences are increased susceptibility towards other DNA damaging agents and endogenous mutagens. Furthermore, cadmium induces cell proliferation, inactivates negative growth stimuli, such as the tumor suppressor protein p53, and provokes resistance towards apoptosis. Particularly the combination of these multiple mechanisms may give rise to a high degree of genomic instability in cadmium-adapted cells, relevant not only for tumor initiation, but also for later steps in tumor development. Future research needs to clarify the relevance of these interactions for low exposure conditions in humans.