The first category is focused on the cytoskeleton and the centrosome as targets of toxic chemicals. The centrosome is the nucleating center of the microtubules and therefore, it is thought that centrosome damage causes deleterious effects on cells via dysfunction of the microtubules. Studies also have shown that the centrosome plays a role as a dynamic center in which various factors regulating the cell cycle are localized. Recently, we found that dimethylarsinic acid, estrogens, such as diethylstilbestrol and estradiol, and methylmercury were effective inducers of centrosome abnormality and multipolar spindles. These findings have great importance when we consider the mechanism of genomic instability, such as aneuploidy and polyploidy, often seen in cancer.

The second category is focused on the mechanism of the central nerve system disorder caused by diphenylarsine acid, which was identified as a groundwater pollutant in Kamisu, Ibaraki. After searching of two-dimensional gel electrophoresis, glutaminase was identified as one of the candidate target molecules of the diphenylarsine acid. The mechanisms of expressional control of glutaminase by DPAA and the relations with the central nerve system disorder are now investigated.

The third category relates to epigenetic modification of histone by toxic chemicals. We found inorganic arsenite iAs(III) induced phosphorylation and methylation of histone H3. As epigenetic modification of histone is known to regulate gene expressions, we are investigating the relationship between histone modifications and cytotoxicity by iAs(III).

Senior
Assistant
Professor