7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic metabolites of pyrrolizidine alkaloids.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev
; 35(2): 69-83, 2017 04 03.
Article
en En
| MEDLINE
| ID: mdl-28418776
ABSTRACT
Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Metabolism of PAs in vivo generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts that have been proposed to be responsible for PA-induced liver tumor formation in rats. In this present study, we determined that the same set of DHP-DNA adducts was formed upon the incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7-cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor formation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirroles
/
Alcaloides de Pirrolicidina
/
Carcinógenos
/
Cisteína
/
Glutatión
Límite:
Animals
Idioma:
En
Revista:
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev
Asunto de la revista:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos