Oxidative DNA damage induced by S(IV) in the presence of Cu(II) and Cu(I) complexes

The DNA damage induced by S(IV) in the presence of some Cu(II) complexes in air saturated solution was investigated. The addition of S(IV) to an air saturated solution containing CuII GGA (GGA = glycylglycyl-L-alanine), CuII G3 (G3 = triglycine) or CuII G4 (G4 = tetraglycine) and Ni(II) traces, causes rapid formation of the respective Cu(III) complex, with simultaneous O2 uptake and S(IV) oxidation. SO3•- and HO• were detected by EPR-spin trapping experiments. The DNA strand breaks were attributed to the oxysulfur radicals formed. In the reduction of Cu(II)/BCA (BCA = 4,4' dicarboxy-2-2'-biquinoline) by S(IV), with CuI BCA complex formation, there is the possible formation of carbon centered radical of BCA or peroxyl radical (ROO•) capable of oxidizing DNA bases. The intensity of DNA damage in the presence of these Cu(II) complexes and S(IV) (10-300 µmol L-1) followed the order: CuII BCA ∼ CuII G4 ∼ Cu(II) (added as Cu(NO3)2) > CuII G3 ∼ CuII GGA. Specifically for CuII BCA the damage occurred even at lower S(IV) concentration (0.1 µmol L-1). For the Cu(II) complexes with glycylglycylhistidine, glycylhistidylglycine, glycylhistidyllysine and glycylglycyltyrosylarginine the Cu(III) formation and the DNA damage was not observed.O dano ao DNA induzido por S(IV) na presença de alguns complexos de Cu(II) em soluções saturadas com ar foi investigado. A adição de S(IV) a uma solução saturada com ar contendo CuII GGA (GGA = glicilglicil-L-alanina), CuII G3 (G3 = triglicina) ou CuII G4 (G4 = tetraglicina) e traços de Ni(II) origina a formação rápida do respectivo complexo de Cu(III), com o simultâneo consumo de oxigênio e a oxidação de S(IV). SO3•- e HO• foram detectados por experimentos de EPR-spin trapping. As quebras das fitas de DNA foram atribuídas aos radicais de óxido de enxofre formados. Na redução de Cu(II)/BCA (BCA = 4,4' dicarboxi-2-2'-biquinolina) por S(IV), com a formação do complexo CuI BCA, há a possível formação de um radical centrado em carbono do BCA ou um radical peróxido (ROO•), capazes de oxidar as bases de DNA. A intensidade do dano ao DNA na presença desses complexos de Cu(II) e S(IV) (10-300 µmol L-1) seguiu a ordem: CuII BCA ∼ CuII G4 ∼ Cu(II) (adicionado como Cu(NO3)2) > CuII G3 ∼ CuII GGA. Especialmente para o CuII BCA, o dano ocorreu mesmo em concentrações baixas de S(IV) (0,1 µmol L-1). Para os complexos de Cu(II) com glicilglicilhistidina, glicilhistidilglicina, glicilhistidillisina e glicilgliciltirosilarginina a formação de Cu(III) e o dano do DNA não foram observados.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (CNPq) (Brazilian Agencies

Further studies on the synergistic effect of Ni(II) and Co(II) ions on the sulfite induced autoxidation of Cu(II) penta and hexaglycine complexes

The autoxidation of Cu(II)/penta and hexaglycine complexes at pH = 9 is very slow showing a large induction period (about 4 h). The presence of S(IV) practically does not affect the rate of this reaction. Addition of small amounts of Ni(II) or Co(II) increases significantly the reaction rate and the effectiveness of Cu(III) formation, the induction period becomes as short as 0.5 s. The observed rate constant for Cu(III) formation also depends on the S(IV) concentration. The mechanism is discussed based on the available literature information and involves a radical chain and redox cycling of the metal ion complexes

Lesões em DNA induzidas pela autoxidação de S(IV) na presença de íons metálicos de transição

The oxidation of sulfite catalyzed by transition metal ions produces reactive oxysulfur species that can damage plasmid and isolated DNA in vitro. Among the four DNA bases, guanine is the most sensitive to one-electron oxidation promoted by the species formed in the autoxidation of sulfite (HSO5-, HO?, SO3?-, SO4?- and SO5?-) due to its low reduction potential and ability to bind transition metal ions capable to catalyze oxidative processes. Some oxidative DNA lesions are promutagenic and oxidative DNA damage is proposed to play a crucial role in certain human pathologies, including cancer