Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Breaks in Double-Strand DNA by Cu(II) Complexes of Etoposide (VP-16) and Its Derivatives, as Evaluated by S1 Nuclease Treatment
Riichi TAWAMasashi TAKAMIYasuhiro IMAKURAKuo-Hsiung LEEHiromu SAKURAI
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1997 Volume 20 Issue 9 Pages 1002-1005

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Abstract
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-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.
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© The Pharmaceutical Society of Japan
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