Amplification of bleomycin-induced DNA cleavage by pyrrole triamide.
We investigated the amplification of bleomycin-induced DNA cleavage by synthetic pyrrole triamide (PyPyPy) using 32P-labeled DNA fragments obtained from human genes. Peplomycin, a kind of bleomycins, plus Fe(II) caused DNA cleavage at the 5'-GC-3' and 5'-GT-3' sequences (damaged bases are underlined). The addition of PyPyPy enhanced the cleavage at cytosine and thymine residues 3' to consecutive guanines, particularly at the 5'-GGGGC-3' and 5'-GGGGT-3' sequences. These results suggest that PyPyPy binds to DNA to induce its conformational change, resulting in alteration of the site specificity and amplification of DNA cleavage. The present study on amplifiers of antitumor drugs would show a novel approach to the establishment of more effective chemotherapy.
Hiraku
Y
Y
Department of Hygiene, Mie University School of Medicine, Japan.
Oikawa
S
S
Kawanishi
S
S
Sugiyama
H
H
Saito
I
I
D001761:Bleomycin / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D011905:Genes, ras; D006801:Humans; D007501:Iron; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D017663:Peplomycin / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*
D009838:Oligodeoxyribonucleotides; D011758:Pyrroles; C409814:pyrrole triamide; D001761:Bleomycin; D017663:Peplomycin; D004247:DNA; D007501:Iron