Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, 30 Pildong-ro 1-gil, Jung-gu, Seoul 100-715, Republic of Korea.
Int J Hyg Environ Health. 2013 Aug;216(5):587-98. doi: 10.1016/j.ijheh.2013.02.010. Epub 2013 Mar 13.
Heavy metals that are harmful to humans include arsenic, cadmium, chromium, lead, mercury, and nickel. Some metals or their related compounds may even cause cancer. However, the mechanism underlying heavy metal-induced cancer remains unclear. Increasing data show a link between heavy metal exposure and aberrant changes in both genetic and epigenetic factors via non-targeted multiple toxicogenomic technologies of the transcriptome, proteome, metabolome, and epigenome. These modifications due to heavy metal exposure might provide a better understanding of environmental disorders. Such informative changes following heavy metal exposure might also be useful for screening of biomarker-monitored exposure to environmental pollutants and/or predicting the risk of disease. We summarize advances in high-throughput toxicogenomic-based technologies and studies related to exposure to individual heavy metal and/or mixtures and propose the underlying mechanism of action and toxicant signatures. Integrative multi-level expression analysis of the toxicity of heavy metals via system toxicology-based methodologies combined with statistical and computational tools might clarify the biological pathways involved in carcinogenic processes. Although standard in vitro and in vivo endpoint testing of mutagenicity and carcinogenicity are considered a complementary approach linked to disease, we also suggest that further evaluation of prominent biomarkers reflecting effects, responses, and disease susceptibility might be diagnostic. Furthermore, we discuss challenges in toxicogenomic applications for toxicological studies of metal mixtures and epidemiological research. Taken together, this review presents toxicogenomic data that will be useful for improvement of the knowledge of carcinogenesis and the development of better strategies for health risk assessment.
重金属对人类有害，包括砷、镉、铬、铅、汞和镍。一些金属或其相关化合物甚至可能导致癌症。然而，重金属致癌的机制尚不清楚。越来越多的数据表明，通过非靶向的转录组、蛋白质组、代谢组和表观基因组的多个毒理基因组技术，重金属暴露与遗传和表观遗传因素的异常变化之间存在联系。由于重金属暴露而导致的这些变化可能提供了对环境紊乱的更好理解。重金属暴露后的这些信息变化也可能有助于筛选生物标志物监测的环境污染物暴露和/或预测疾病风险。我们总结了基于高通量毒理基因组学技术的进展以及与个体重金属和/或混合物暴露相关的研究，并提出了潜在的作用机制和毒物特征。通过基于系统毒理学的方法学与统计和计算工具相结合，对重金属毒性进行综合多层次表达分析，可能阐明致癌过程中涉及的生物学途径。尽管体外和体内标准终点测试的致突变性和致癌性被认为是与疾病相关的互补方法，但我们还建议，进一步评估反映效应、反应和疾病易感性的突出生物标志物可能具有诊断意义。此外，我们还讨论了金属混合物毒理学研究和流行病学研究中毒理基因组应用的挑战。总之，本综述提供了毒理基因组数据，这些数据将有助于提高对致癌作用的认识，并制定更好的健康风险评估策略。
