o-Anisidine Dimer, 2-Methoxy-N4-(2-methoxyphenyl) Benzene-1,4-diamine, in Rat Urine Associated with Urinary bladder Carcinogenesis
| Autor: | Shuichi Masuda, Masako Ochiai, Kumiko Ogawa, Michio Sato, Yuko Shimamura, Yukari Totsuka, Takuma Kobayashi, Shinji Kishimoto, Kenji Watanabe, Yuta Tsunematsu, Yuya Tajima, Noriyuki Miyoshi, Keiji Wakabayashi, Kohei Matsushita, Takeshi Toyoda, Takanori Yamada, Takeji Takamura-Enya |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Urinary bladder DNA damage Metabolite Urinary system o-Anisidine General Medicine 010501 environmental sciences Toxicology medicine.disease_cause 01 natural sciences Molecular biology 03 medical and health sciences chemistry.chemical_compound medicine.anatomical_structure chemistry In vivo medicine bacteria Carcinogen Genotoxicity 030304 developmental biology 0105 earth and related environmental sciences |
| Zdroj: | Chemical Research in Toxicology. 34:912-919 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/acs.chemrestox.0c00536 |
| Popis: | Monocyclic aromatic amines, o-toluidine (o-Tol) and its structural analog o-anisidine (o-Ans), are IARC Group 1 and Group 2A urinary bladder carcinogens, respectively, and are involved in metabolic activation and DNA damage. Our recent study revealed that 2-methyl-N4-(2-methylphenyl) benzene-1,4-diamine (MMBD), a p-semidine-type homodimer of o-Tol, was detected and identified in an in vitro reaction of o-Tol with S9 mix and in vivo urinary samples of o-Tol-exposed rats. Potent mutagenic, genotoxic, and cytotoxic activities were reported with MMBD, suggesting its involvement in urinary bladder carcinogenesis. However, it remains unknown whether o-Ans is converted to active metabolites to induce DNA damage in a similar manner as o-Tol. In this study, we report that a novel o-Ans metabolite, 2-methoxy-N4-(2-methoxyphenyl) benzene-1,4-diamine (MxMxBD), a dimer by head-to-tail binding (p-semidine form), was for the first time identified in o-Ans-exposed rat urine. MxMxBD induced a stronger mutagenicity in N-acetyltransferase overexpressed Salmonella typhimurium strains and potent genotoxicity and cytotoxicity in human bladder carcinoma T24 cells compared with o-Ans. These results suggest that MxMxBD may to some extent contribute toward urinary bladder carcinogenesis. In addition to homodimerization, such as MxMxBD, heterodimerizations were observed when o-Ans was coincubated with o-Tol or aniline (Ani) in in vitro reactions with S9 mix. This study highlights the important consideration of homodimerizations and heterodimerizations of monocyclic aromatic amines, including o-Ans, o-Tol, and Ani, in the evaluation of the combined exposure risk of bladder carcinogenesis. |
| Databáze: | OpenAIRE |
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