Metabolism and effects of acetoaceto--toluidine in the urinary bladder of humanized-liver mice.

Occupational exposure to aromatic amines is a major risk factor for urinary bladder cancer. Our previous studies showed that acetoaceto--toluidine, which is produced using -toluidine as a raw material, promotes urinary bladder carcinogenesis in rats. We also found high concentrations of -toluidine, a human bladder carcinogen, in the urine of acetoaceto--toluidine-treated rats, indicating that urinary -toluidine derived from acetoaceto--toluidine may play an important role in bladder carcinogenesis.

Development of a genotoxicity/carcinogenicity assessment method by DNA adductome analysis.

Safety evaluation is essential for the development of chemical substances. Since in vivo safety evaluation tests, such as carcinogenesis tests, require long-term observation using large numbers of experimental animals, it is necessary to develop alternative methods that can predict genotoxicity/carcinogenicity in the short term, taking into account the 3Rs (replacement, reduction, and refinement). We established a prediction model of the hepatotoxicity of chemicals using a DNA adductome, which is a comprehensive analysis of DNA adducts that may be used as an indicator of DNA damage in the liver.

Urinary bladder carcinogenic potential of 4,4'-methylenebis(2-chloroaniline) in humanized-liver mice.

Occupational exposure to 4,4'-methylenebis(2-chloroaniline) (MOCA) has been linked to an increased risk of bladder cancer among employees in Japanese plants, indicating its significance as a risk factor for urinary bladder cancer. To investigate the role of MOCA metabolism in bladder carcinogenesis, we administered MOCA to non-humanized (F1-TKm30 mice) and humanized-liver mice for 4 and 28 wk. We compared MOCA-induced changes in metabolic enzyme expression, metabolite formation, and effects on the urinary bladder epithelium in the 2 models.

A novel support vector machine-based 1-day, single-dose prediction model of genotoxic hepatocarcinogenicity in rats.

The development of a rapid and accurate model for determining the genotoxicity and carcinogenicity of chemicals is crucial for effective cancer risk assessment. This study aims to develop a 1-day, single-dose model for identifying genotoxic hepatocarcinogens (GHCs) in rats. Microarray gene expression data from the livers of rats administered a single dose of 58 compounds, including 5 GHCs, was obtained from the Open TG-GATEs database and used for the identification of marker genes and the construction of a predictive classifier to identify GHCs in rats.