| RRC ID |
72433
|
| 著者 |
Kobayashi T, Toyoda T, Tajima Y, Kishimoto S, Tsunematsu Y, Sato M, Matsushita K, Yamada T, Shimamura Y, Masuda S, Ochiai M, Ogawa K, Watanabe K, Takamura-Enya T, Totsuka Y, Wakabayashi K, Miyoshi N.
|
| タイトル |
o-Anisidine Dimer, 2-Methoxy-N4-(2-methoxyphenyl) Benzene-1,4-diamine, in Rat Urine Associated with Urinary bladder Carcinogenesis.
|
| ジャーナル |
Chem Res Toxicol
|
| Abstract |
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.
|
| 巻・号 |
34(3)
|
| ページ |
912-919
|
| 公開日 |
2021-3-15
|
| DOI |
10.1021/acs.chemrestox.0c00536
|
| PMID |
33587850
|
| MeSH |
Animals
Carcinogens / chemistry
Carcinogens / toxicity*
Male
Molecular Structure
Mutagenicity Tests*
Rats
Rats, Inbred F344
Urinary Bladder Neoplasms / chemically induced*
|
| IF |
3.184
|
| リソース情報 |
| ヒト・動物細胞 |
T24(RCB2536) |
