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 hydro xyl radicals (. OH) generated by Cu(II) complexes of podophyllotoxin ( FD)-related compounds were evaluated using S1 nuclease digestion. Cu(I I) complexes of VP-16 (etoposide, oxin-9-(4,6-O-ethylidene-beta-D-gluc opyranoside)), 4'-demethylepi-PD (DEPD), and syringic acid (SA) exhibi ted both ssb and ds breaks (dsb) in ColE1-HaeII and pBR322-BglI DNA fr agments, in which the number of ssb was found to be more than three ti mes and four times greater than that of dsb, respectively. Cytosine (C )-methylation of cytosine-guanine doublet (CpG) in pBR322-BglI DNA inh ibited bath ssb and dsb within DNA segments by . OH generated by the C u(II) complexes.