毒理基因组学研究进展

Progress in toxicogenomics

毒理基因组学是利用最新的基因组学技术来进行毒理学研究的新兴学科。它能够快速全面地检测出化合物和生物体相互作用后的全基因组表达的变化,再通过生物信息学的方法对化合物的毒性进行定性分析。它可以为传统毒理学检测筛选更多的生物学标志物,解释有毒物质的致毒机理,降低风险评价的不确定性。但是,毒理基因组学还存在许多问题:如实验设计不统一,分析理论不完善,检测费用太昂贵等。其中最主要的理论问题在于,虽然人们早已认识到毒理基因组学最大的优势是可对毒性进行较全面的分类和预测,但是已有的研究仍然集中在生物标志物的筛选和致毒机理的解释上,而没有充分利用全基因组变化的信息,因为理论上除了实验误差引入的基因表达变化以外的变化都是化合物和生物体相互作用的结果。要解决这些问题,新发现的microRNA毒理基因组和动态基因表达图谱的研究可能是一个潜在方向。总体来说,目前毒理基因组学只能作为风险评价的参考,但是它最终将为风险评价提供有力的理论依据和准确预测,提高风险评价的可靠性。

Toxicogenomics is an emerging discipline that uses the latest genomic technologies for toxicology studies.It can quickly detect the alteration of genome-wide gene expression resulting from the interaction of chemical compounds and organisms,and the toxicity of compounds can be qualitatively analyzed through bioinformatics.Additionally,toxicogenomic approaches allow screening of more biomarkers for traditional toxicity testing,explain the mechanisms of toxicity,and reduce the uncertainty of risk assessment.However,problems such as non-uniform experimental design,flawed analysis theory,and relatively expensive testing costs restrict this field＇s development.Furthermore,the greatest concern faced by toxicogenomics is the inconsistency between its purpose and the methods in which it is carried out.It has long been recognized that the main objective of toxicogenomics,and also its most attractive advantage,is to conduct a more comprehensive classification and prediction of toxicities,but the published research works continue to focus mainly on biomarker screening and interpretation of toxicity mechanisms.And the current toxicity prediction studies are based on the extraction of a compound-specific ＇signature＇,a concept originated from tumor diagnosis,which comprises a group of marker genes and their expression level at defined treatment conditions.This method ignores the information of the dynamic changes of gene expression,which reflect the true and compound-specific gene expression pattern in theory.The newly developing microRNA toxicogenomics and dynamic analysis of gene expression profile could potentially address these problems.Overall,current toxicogenomics can only supply additional reference data for the risk assessment,but will eventually provide a strong theoretical basis and accurate prediction,and improve the reliability of risk assessment.