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'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyra noside)), 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.
Tawa
R
R
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan.
Takami
M
M
Imakura
Y
Y
Lee
K H
KH
Sakurai
H
H
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004249:DNA Damage; D019175:DNA Methylation; D005047:Etoposide / Q000737:chemistry*; D005069:Evaluation Studies as Topic; D010957:Plasmids / Q000235:genetics; D015719:Single-Strand Specific DNA and RNA Endonucleases
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D003300:Copper; D015719:Single-Strand Specific DNA and RNA Endonucleases