Breaks in Double-Strand DNA by Cu(II) Complexes of Etoposide (VP-16) and Its Derivatives, as Evaluated by S1 Nuclease Treatment.

Single-strand breaks (ssb) in double-strand (ds) DNA produced by hydroxyl radicals ( OH) generated by Cu(II) complexes of podophyllotoxin (PD)-related compounds were evaluated using S1 nuclease digestion. Cu(II) complexes of VP-16 (etoposide, 4'-mdemethylepipodophyllotoxin-9-(4,6-O-ethylidene-β-D-glucopyranoside)), 4'-demethylepi-PD (DEPD), and syringic acid (SA) exhibited both ssb and ds breaks (dsb) in ColE1-HaeII and pBR322-BglI DNA fragments, in which the number of ssb was found to be more than three times and four times greater than that of dsb, respectively. Cytosine (C)-methylation of cytosine-guanine doublet (CpG) in pBR322-BglI DNA inhibited both ssb and dsb within DNA segments by.OH generated by the Cu(II) complexes