| Revista: | Brazilian Journal of Pharmaceutical Sciences |
| Base de datos: | PERIÓDICA |
| Número de sistema: | 000452164 |
| ISSN: | 1984-8250 |
| Autores: | Kim, Min Young1 |
| Instituciones: | 1Jeju National University, College of Applied Life Science, Jeju. Corea del Sur |
| Año: | 2022 |
| Volumen: | 58 |
| País: | Brasil |
| Idioma: | Inglés |
| Tipo de documento: | Artículo |
| Enfoque: | Experimental, aplicado |
| Resumen en inglés | The purpose of the current work was to assess a possible role of cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) in the metabolic activation of 2,6-dimethylaniline (2,6-DMA) and also clarify the function of DNA repair in affecting the ultimate mutagenic potency. Two cell lines, nucleotide excision repair (NER)-deficient 5P3NAT2 and proficient 5P3NAT2R9 both expressing CYP1A2 and NAT2, were treated with 2,6-DMA for 48 h or its metabolites for 1 h. Cell survival determined by trypan blue exclusion and MTT assays, and 8-azaadenine-resistant mutants at the adenine phosphoribosyltransferase (aprt) gene locus were evaluated. 5P3NAT2 and 5P3NAT2R9 cells treated with 2,6-DMA and its metabolites showed a dose-dependent increase in cytotoxicity and mutant fraction; N-OH-2,6-DMA and 2,6-DMAP in serum-free α-minimal essential medium (MEM) are more potent than 2,6-DMA in complete MEM. 5P3NAT2 cells was more sensitive to the cytotoxic and mutagenic action than 5P3NAT2R9 cells. H2DCFH-DA assay showed dose-dependent ROS production under 2,6- DMAP treatment. These findings indicate that the genotoxic effects of 2,6-DMA are mediated by CYP1A2 activation via N-hydroxylation and the subsequent esterification by the phase II conjugation enzyme NAT2, and through the generation of ROS by hydroxylamine and/or aminophenol metabolites. NER status is also an important contributor |
| Disciplinas: | Química |
| Palabras clave: | Bioquímica, N-acetiltransferasa 2. 2,6-dimetilamina, Genotoxicidad, Citocromo P450 |
| Keyword: | Biochemistry, N-Acetyltransferase 2. 2,6-Dimethylaniline, Genotoxicity, Cytochrome P450 |
| Texto completo: | Texto completo (Ver HTML) Texto completo (Ver PDF) |
