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Toxic variability and radiation sensitization by dichlorodiammineplatinum(II) complexes in Salmonella typhimurium
Abstract:
The oxidative coordination compound cis-dichlorodiammineplatinum(II) (cis-DDP) is again shown to be a hypoxic cell radiation sensitizer. The mechanism of cis-DDP-induced radiation sensitization is complex. Results here indicate that cis-DDP sensitization operates in part through reactive free radicals, in part through the interactions of radiation-induced reactive Pt(I) intermediates, and in part through the involvement of thermodynamic and kinetic aspects of Pt(II)-DNA binding during irradiation. For the first time, radiation sensitization by trans-DDP is compared with a sensitizing concentration of cis-DDP within the same study. Both analogs are sensitizers, but with significant differences. Further, irradiated hypoxic solutions of cis-DDP are found to be more toxic than unirradiated solutions.