Gene expression profiling in the rat lung exposed to methacrylamide, sulfolane, 2-iso-propoxyethanol, hydrazine monohydrate and 4-ethylmorpholine. CIBEX accession: CBX210. 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 methacrylamide, sulfolane, 2-iso-propoxyethanol, hydrazine monohydrate and 4-ethylmorpholine independently to male for 28 days repeatedly, prepared multiple tissue samples of each animal, and comprehensively investigated gene expression levels in the lung 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）主要研究化学物质对生物体的影响，其通过生物指标开展相关研究，所用实验方法涵盖生物化学、免疫学与病理学技术，此类方法均需依托适配自身技术特性的多平台检测体系。与之相对，近年来发展的基因组学（genomics）技术可将数千个基因作为检测参数，在单一平台（如基因表达谱分析）中对多种生物学现象进行评估。因此，将基因组学与毒理学相融合，有望开辟化学物质生物学评估的全新研究领域：通过单平台多参数分析，表征不同样本中动物或培养细胞暴露于化学物质后的分子变化。本研究中，我们对雄性大鼠分别重复给予5种化学物质——甲基丙烯酰胺、环丁砜、2-异丙氧基乙醇、一水合肼与4-乙基吗啉，给药周期为28天；随后采集每只大鼠的多组织样本，并通过搭载有约11000种大鼠转录本探针的DNA微阵列（DNA microarray），全面检测肺组织的基因表达水平。我们期望，本研究获得的数据可与既往通过大鼠28天重复经口给药得到的研究成果进行比对，从而助力建立精准评估现有及未来新增化学物质的全新方法体系。