Carbonyl side-chain of catechol compounds is a key structure for the suppression of copper-associated oxidative DNA damage in vitro.
Toxicol Lett
; 199(3): 213-7, 2010 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-20832456
ABSTRACT
Catechol is possibly carcinogenic to humans (International Agency for Research on Cancer, IARC). The key mechanism could include its oxidative DNA-damaging effect in combination with reductive-oxidative metals like Cu. We found that DNA damage was suppressed by introducing an α-carbonyl group to catechol at C4-position to produce carbonyl catechols. During the oxidative DNA-damaging process, catechols but not carbonyl catechols were oxidized to o-quinone; however, coexisting Cu(II) was reduced to Cu(I). Carbonyl catechols were possibly arrested at the oxidation step of semiquinones in the presence of Cu(II). Cu(I)-binding to DNA was stronger than Cu(II)-binding, on the basis of the circular dichroism spectral change. None of the carbonyl catechols induced such change, suggesting sequestration of Cu(I) from DNA. Solid-phase extraction experiments and spectrophotometric analyses showed the formation of semiquinone chelates with Cu(I). Thus, chelate formation could explain the suppression mechanism of the Cu-catechol-dependent DNA damage by terminating the reduction-oxidation cycle. Structural modifications such as introducing an α-carbonyl group to catechol at C4-position would contribute to reducing the risk and improving industrial and medical potentials of aromatic/phenolic compounds sustaining our daily lives.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Catecoles
/
Cobre
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
Toxicol Lett
Año:
2010
Tipo del documento:
Article
País de afiliación:
Japón