Antiproliferative and cytotoxic effect of a novel organotin compound on mammalian cells both in vitro and in vivo

Abstract

Organotin compounds are organometallic compounds showing various toxicological properties. Several organotin compounds also showed an antineoplastic effect. However, their relative mutagenic potential is not well established. In this study Et 2SnCl 2·L [L= N-(2-pyridylmethylene)-4-toluidine] (OTC) has been subjected to investigation for its cytotoxic effect in mouse bone marrow cells (BMCs) and human peripheral blood lymphocyte cells (HPBLs). The SnN bond in OTC is 2.46 Å which is greater than 2.39 Å and therefore, a better formation of tin–DNA complex can be expected. The present data indicate that OTC induced significant delay in cell kinetics and sister chromatid exchanges (SCEs) in both BMCs and HPBLs, whereas, induction of chromosome aberrations was found only in HPBLs. The presence of buthionine sulfoximine (BSO) modulated cellular sensitivity towards OTC in both cell systems. It may be inferred that the OTC could bind on DNA more easily owing to its structural advantage and this may explain the induction of DNA damage and the delay in cell proliferation. Since the cytotoxic effect of OTC is more in glutathione depleted cells, the concentration of OTC may be reduced to get an antitumour effect in GSH-depleted cells and thus minimizes its toxic side effect.