Division of Cellular and Molecular Toxicology

National Institute of Health Sciences(NIHS)

Center for Biological Safety and Research (CBSR)

Research Activity

Applied study for the practical use of toxicogenomics technology(Percellome project)

We have been promoting toxicogenomics study since 2003 as the “Percellome Project”. This Project has been launched to develop a comprehensive gene network for the mechanism-based predictive toxicology. It is based on our original-normalization method which enables to measure the gene expression (the amount of RNA) as copies number per one cell. “Percellome” means Per-one Cell-ome. We build and maintain “Percellome Database”, which is one of the biggest transcriptome database concentrated on single-dose (acute) toxicity and ready to access through the internet without any restriction. Recently, we start a new project to enhance the Percellome Database for repeated-dose toxicity prediction. Right-Top pictures show the concept of our “new model” of repeat-dose animal experiments. This new method can separate the repeated-dose toxicity into two elements, i.e. "baseline" element) and "transit" element). Also, we start the analysis of epigenetics and it could elucidate the mechanism of repeated-dose toxicity. Preliminary, we found that some type of histone modification is important for forming repeated-dose toxicity.

Toxicogenomics research

Study on hazard assessment of nanomaterials (NMs) by inhalation exposure

We invented a unique nanosize-level dispersion method ("Taquann" method; patent obtained), for the severe-controlled exposure experiments. We created a compact and inexpensive inhalation exposure system based on the patent. The point is, the importance of dispersity of nanomaterials in order to detect their toxicity. There are two reasons. One is aggregates/agglomerates of nanomaterials mask nature of their toxicity. Second, from the point of view human exposure scenario, only well dispersed nanomaterials considered to be inhaled. For example, in order to investigate the influence of Aggregates/Agglomerates on lung burden and histopathology, we performed a inhalation exposure study on mice using dispersed and pristine Multi-walled carbon nanotube. The lung burden of dispersed-MWCNT was twice as high as pristine-MWCNT under the same exposure of mass concentration. Histologically, there were not drastic but slight differences in lesion caused by small aggregates/agglomerates in the lungs of Untreated-CNT group.

Hazard assessment of nanomaterials

  • Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube(J Toxicol Sci.,33,105,2008)
  • Multi-walled Carbon Nanotubes and Mesothelioma (ICON)
  • Study on sick-house syndrome: very low-dose inhalation system and behavior analysis

    We are trying to Study on Indoor Air Pollution, especially in view of Sick house/ building syndrome. So what is Sick house/ building syndrome? Generally speaking, the term, Sick house/ building syndrome (SH) is used to describe situations in which building occupants experience acute health and comfort effects that appear to be linked to time spent in a building, but no specific illness or cause can be identified. Symptoms, e.g., headache; dry cough; difficulty in concentrating; fatigue; and sensitivity to odors. The cause of the symptoms is not known. Most of the complainants report relief soon after leaving the building. As the background, toxicity of volatile organic compounds (VOCs) in indoor air, at the levels of Sick House/Building Syndrome (SH), that is the extra-low concentration, is difficult to assess by the ordinary inhalation animal studies; that is histopathological endpoints are negative for toxicity at such concentration level. There was an approximately 1,000 times difference between the concentration of rodent- and human-case! Ministry of Health, Labour, and Welfare of Japan set the guideline values for 13 VOCs shown in this slide. This list include such as formaldehyde, Xylene, Paradichlorobenzene and so on. We apply the Percellome toxicogenomics method to this problem, and interestingly, strong suppression of gene expression of IEGs related to neuronal activity in hippocampus was observed commonly among the three chemicals at a very low human-relevant exposure levels corresponding to the so-called human “sick building syndrome (of the guideline values ). The analysis of emotional & cognitive behavior induced by these indoor VOCs are now in progress.

    research about Sick-building syndrome

    Endocrine disruptor

  • The Endocrine Disruptor Page
  • Advisory Committee on Health Effects of Endocrine Disruptors: The Supplement II to the Intermediary Report