ABSTRACT
For the cytotoxic mechanism of irinotecan, the following TOP-I-mediated steps of functional DNA alterations are of importance:2,4,19-21
1. TOP-I relaxes torsionally strained supercoiled duplex DNA by becoming covalently linked by its tyrosine hydroxyl group (position 723) to the 3’-phosphate at the DNA break site, resulting in an enzyme-linked single-strand nick in the phosphodiester backbone of DNA.
