Interactions of surface-confined DNA with electroreduced mitomycin C comparison with acid-activated mitomycin C.
The anticancer activity of the antineoplastic drug mitomycin C (MC) was investigated using transfer stripping cyclic voltammetry (TSCV) with single-stranded DNA-modified hanging mercury drop electrode (HMDE). Reductive activation of MC is necessary for drug covalent binding to DNA, and we have found that some potential-controlled interactions of MC with DNA occur at the electrode, i.e. MC can be activated by electroreduction. Acid and electroreductive MC activations were compared and different adducts were subsequently generated, suggesting that the drug can bind to DNA in more than one way. Under conditions of acid activated MC, a monofunctional adduct between C-1 of MC and N-7 of guanine was formed on the electrode surface, reduced at - 0.44 V (vs. SCE). However, when the DNA-modified electrode was immersed in a MC solution and potentials corresponding to the quinone moiety reduction (- 0.3 V or more negative vs. SCE) were applied, an intrastrand bifunctional adduct between C-1 and C-10 of MC and two N-7 of a pair of adjacent guanines in ssDNA were formed at the electrode, reduced at - 0.49 V, i.e. 50 mV more negative than the monoadduct. The results presented in this paper show for the first time electrochemical detection of DNA-MC adducts at the hanging mercury drop electrode.
Perez
P
P
Departamento de Quimica Fisica, Universidad de Alcalá de Henares, Madrid, Spain.
Teijeiro
C
C
Marin
D
D
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D002417:Cattle; D018736:DNA Adducts / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D016685:Mitomycin / Q000378:metabolism*; D011199:Potentiometry; D013499:Surface Properties
D000903:Antibiotics, Antineoplastic; D018736:DNA Adducts; D004277:DNA, Single-Stranded; D016685:Mitomycin