室内揮発性有機化学物質の極低濃度下における吸入曝露の際のマウス中枢神経系への影響

抄録

　Toxicity of volatile organic compounds (VOCs) in indoor air, such as formaldehyde (FA), xylene (Xy) and p-dichlorobenzene (pDB), at the levels of Sick House/Building Syndrome (SHS) is difficult to assess by the ordinary inhalation animal studies; histopathological endpoints are negative for toxicity at such concentration levels. Here we applied our Percellome Toxicogenomics Project that has been launched to develop a comprehensive gene network for the mechanism-based predictive toxicology using time- and dose-dependent transcriptomic responses induced by a chemical in mice. For this purpose, a normalization method designated as “Percellome” is developed (BMC Genomics 7:64, 2006) to generate mRNA expression values in “copy numbers per one cell” from microarrays and Q-PCR. Here, we report that the Percellome analysis is capable of predicting functional insults by short-term inhalation at SHS-level concentration.

　Lung, liver and hippocampus were analyzed. In contrast to the slight transcriptomic changes in lungs and livers, a　remarkable finding common to the three chemicals were the strong suppression of gene expression related to neuronal activity in hippocampus, i.e. the immediate early genes (IEGs) including Arc, Dusp1 and Fos. Review of the lung and liver gene profile pointed out a candidate cytokine upstream of IEGs. Our finding may be considered as a first substantial data that would explain the indefinite or unidentified complaint in SHS patients. The analysis of emotional & cognitive behavior induced by these indoor VOCs will be presented.