1. Visualization of the distribution of anthraquinone components from madder roots in rat kidneys by desorption electrospray ionization-time-of-flight mass spectrometry imaging.

Imaging mass spectrometry with desorption electrospray ionization (DESI-MSI) revealed that several anthraquinone components showed different distribution patterns in rat kidney after administration of Madder color. Furthermore, we found that mutagenic components, lucidine and rubiadine, are specifically distributed in the outer stripe of the outer medulla, which is the carcinogenic target site of Madder color. (Food. Chem. Toxicol., 161: 112851, 2022)

2. Chromosome aberrations induced by the non-mutagenic carcinogen acetamide involve in rat hepatocarcinogenesis through micronucleus formation in hepatocytes.

Liver micronucleus assay revealed that the rat hepatocarcinogen acetamide induces chromosomal aberrations specifically in the liver. We also found that large micronuclei, histopathologically observed as cytoplasmic inclusions, exhibit loss of nuclear envelope-related proteins and accumulation of DNA damage. (Arch. Toxicol., 95: 2851-2865, 2021)

3. The role of DNA polymerase z in benzo[a]pyrene-induced mutagenesis in the mouse lung.

Using Rev3lL^2610M gpt delta mice expressing DNA polymerase z (Polz) with low replication fidelity, we have shown that Polz exerts nucleotide incorporation and mismatch extension against benzo[a]pyrene-induced DNA damage. (Mutagenesis, 47: 44-52, 2021)

4. Lack of in vivo mutagenicity of acetamide in a 13-week comprehensive toxicity study using F344 gpt delta rats.

A comprehensive toxicity study using gpt delta rats revealed that the rat hepatocarcinogen acetamide has hepatotoxicity. On the other hand, no changes in mutation frequency was observed in the liver, suggesting that mutagenicity is unlikely to be involved in the hepatocarcinogenic process. (Toxicol.Sci., 177:431-440, 2020)

5. Molecular Pathological Differences in Global Gene Expression between Two Sustained Proliferative Lesions, Nodular Regenerative Hepatocellular Hyperplasia and Hepatocellular Adenoma, in Mice.

Complementary DNA microarray analysis revealed that the proliferative lesions, nodular regenerative hepatocellular hyperplasia and hepatocellular adenoma, observed in the mouse liver after long-term administration of piperonyl butoxide had different molecular pathological features. (Toxicol. Pathol., 47: 44-52, 2019)

6. Effects of inhibition of hepatic sulfotransferase activity on renal genotoxicity induced by lucidin-3-O-primeveroside.

We have shown that lucidine-3-O- primeveroside, a component of madder color, is metabolically activated by hepatic sulfotransferase, and induced DNA damage and gene mutation in the kidney. (J. Appl. Toxicol., 39:650-657, 2019)

7. DNA modifications that do not cause gene mutations confer the potential for mutagenicity by combined treatment with food chemicals.

Combined treatment of estragole and flumequine to gpt delta mice revealed that changes in the intracellular microenvironment enhanced mutagenicity of estragole. (Food Chem. Toxicol., 129:144-152, 2019)