DNA cleavages of bleomycin-transition metal complexes induced by reductant, hydrogen peroxide, and ultraviolet light: characteristics and biological implication.

In DNA strand scission of Mn-, Co-, and Fe-complexes of bleomycin-A2 (BLM), the Mn-BLM and Fe-BLM complex systems showed prominent DNA cleavage activity in combination with reductant, hydrogen peroxide, and ultraviolet light. The sequence-specific cleavage modes of the two metallobleomycins were remarkably similar. The present results suggest that the DNA breakage mechanism of the Mn-BLM resembles that of the Fe-BLM, and that Mn as well as Fe is an effective metal cofactor in the BLM drug action. In contrast, the Co -BLM complex system significantly degraded DNA only by irradiation of UV light. The DNA breakage of the tallysomycin(TLM)- and peplomycin(PEM)-metal complexes has also been investigated by nucleotide sequence analysis.