Interaction of tributyltin(IV) chloride and a related complex [Bu3Sn(LSM)] with rat leukocytes and erythrocytes:: Effect on DNA and on plasma membrane

The discovery of the antitumor activity of cisplatin led several research groups to investigate the possible therapeutic applications of other metal-based compounds. Organotin(IV) complexes have been developed from organotin compounds that were employed in industry and agriculture as stabilizers and pesticides, respectively. A careful choice of the ligand coordinated to an organotin(IV) fragment can modulate the activity of the organotin(IV) complex and minimize its drawbacks. With this aim, the tributyltin(IV) complex [Bu3Sn(LSM)] (LSM=bis(1-methyl-1H-imidazol-2-ylthio)acetate) was synthesized and its in vitro effects on rat blood cells were compared with those of the analogous tributyltin(IV) compound without the anionic ligand. Comet-assay results show that both the tributyltin(IV) chloride (TBTC) and the complex [Bu3Sn(LSM)] can induce DNA damage in leukocytes, but a stronger effect was observed in the presence of the organotin(IV) complex. Moreover, lipid-hydroperoxide formation in leukocyte plasma membranes increases more in the presence of [Bu3Sn(LSM)] compared with TBTC, while TBTC can change the lipid order and packing of leukocytes and, partially, erythrocyte plasma membranes. The treatment of whole blood with these two compounds shows a preferential oxidative effect of TBTC on erythrocyte plasma membranes and erythrocyte oxidative processes, which influence the induction of DNA damage in leukocytes. The different hydrophobic characters and the different extents of steric hindrance of TBTC and [Bu3Sn(LSM)l influence the capacity of the two compounds to cross the plasma membrane and affect the pathways that lead to DNA damage. (C) 2008 Elsevier B.V. All rights reserved.