1 Department of Radiation Biology and Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
2 Department of Cellular and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Hum Exp Toxicol. 2019 Sep;38(9):1031-1059. doi: 10.1177/0960327119851253. Epub 2019 May 22.
Lead (Pb) toxicity is a public health problem affecting millions worldwide. Advances in 'omic' technology have paved the way to toxico-genomics which is currently revolutionizing the understanding of interindividual variations in susceptibility to Pb toxicity and its functional consequences to exposure. Our objective was to identify, comprehensively analyze, and curate all the potential genetic and epigenetic biomarkers studied to date in relation to Pb toxicity and its association with diseases. We screened a volume of research articles that focused on Pb toxicity and its association with genetic and epigenetic signatures in the perspective of occupational and environmental Pb exposure. Due to wide variations in population size, ethnicity, age-groups, and source of exposure in different studies, researchers continue to be skeptical on the topic of the influence of genetic variations in Pb toxicity. However, surface knowledge of the underlying genetic factors will aid in elucidating the mechanism of action of Pb. Moreover, in recent years, the application of epigenetics in Pb toxicity has become a promising area in toxicology to understand the influence of epigenetic mechanisms such as DNA methylation, chromatin remodeling, and small RNAs for the regulation of genes in response to Pb exposure during early life. Growing evidences of ecogenetic understanding (both genetic and epigenetic processes) in a dose-dependent manner may help uncover the mechanism of action of Pb and in the identification of susceptible groups. Such studies will further help in refining uncertainty factors and in addressing risk assessment of Pb poisoning.
铅(Pb)中毒是一个影响全球数百万人的公共卫生问题。“组学”技术的进步为毒代基因组学铺平了道路,毒代基因组学目前正在彻底改变人们对个体对 Pb 毒性易感性的个体差异及其对暴露的功能后果的理解。我们的目的是识别、全面分析和整理迄今为止所有与 Pb 毒性及其与疾病的关联有关的潜在遗传和表观遗传生物标志物的研究。我们筛选了大量研究文章,这些文章从职业和环境 Pb 暴露的角度关注 Pb 毒性及其与遗传和表观遗传特征的关系。由于不同研究中人群规模、种族、年龄组和暴露源的广泛差异,研究人员继续对遗传变异在 Pb 毒性中的影响持怀疑态度。然而,对潜在遗传因素的基本了解将有助于阐明 Pb 的作用机制。此外,近年来,表观遗传学在 Pb 毒性中的应用已成为毒理学领域的一个有前途的领域,以了解表观遗传机制(如 DNA 甲基化、染色质重塑和小分子 RNA)对基因的调控作用,以响应 Pb 暴露在生命早期。越来越多的关于生态遗传学的理解(遗传和表观遗传过程)的证据表明,这种理解与剂量呈正相关,这可能有助于揭示 Pb 的作用机制,并确定易感人群。此类研究将有助于进一步阐明不确定性因素,并解决 Pb 中毒的风险评估问题。