Gene expression profiling in the rat spleen exposed to o-dichlorobenzene,3,4-xylidine ,N-methylaniline ,tolylene diisocyanate , and 2-(diibutylamino)ethanol. CIBEX accession: CBX153. Rattus norvegicus

Toxicology principally investigates the influence of chemical substances onto living organisms by use of biological indicators detected by experimental methods including biochemical, immunological, and pathological approaches that require method-specific multiple platforms. In contrast, recently developed genomics enables to employ thousands of genes as parameters to assess diverse biological phenomena on a single platform such as gene expression profiling. Thus, the integration of genomics into toxicology should exploit novel fields for the biological assessment of substances, describing alterations after exposure of substances to animals or cultured cells with multiple parameters in a single platform across diverse specimens. In this study, we administered five chemical substances o-dichlorobenzene,3,4-xylidine ,N-methylaniline ,tolylene diisocyanate , and 2-(diibutylamino)ethanol independently to male for 28 days repeatedly, prepared multiple tissue samples of each animal, and comprehensively investigated gene expression levels in the spleen with DNA microarrays containing probes representing approximately 11,000 species of rat transcripts. We expect the data obtained in this study may contribute to establish novel accurate approaches for the assessment of chemical substances existing and generated in the future by comparing with the previously accumulated findings obtained by repeated dose 28-day oral administration to rats.

毒理学（Toxicology）主要通过实验方法检测得到的生物指标，研究化学物质对生物体的影响；此类实验手段涵盖生物化学、免疫学及病理学途径，且均需依托方法专属的多平台技术体系。与之相对，近年发展的基因组学可依托数以千计的基因作为参数，在单一平台上评估多种生物学现象，例如基因表达谱分析（gene expression profiling）。因此，将基因组学与毒理学相融合，有望开拓化学物质生物学评估的全新领域：通过单平台多参数分析，刻画化学物质暴露于动物或培养细胞后，多样本中的分子变化特征。本研究对5种化学物质——邻二氯苯（o-dichlorobenzene）、3,4-二甲苯胺（3,4-xylidine）、N-甲基苯胺（N-methylaniline）、甲苯二异氰酸酯（tolylene diisocyanate）及2-(二丁基氨基)乙醇（2-(diibutylamino)ethanol）——分别对雄性大鼠开展为期28天的反复染毒，采集每只大鼠的多份组织样本，并采用搭载约11000种大鼠转录本探针的DNA微阵列（DNA microarray），全面分析脾脏组织的基因表达水平。本研究所得数据，可通过与既往大鼠28天经口反复染毒的累积研究结果进行比对，有望为现有及未来新型化学物质的评估建立精准的全新技术路径。