THE EFFECT OF ORGANOMETALS ON CELLULAR-SHAPE AND CELL-CYCLE

The biological effects of organometals are of great concern because of their toxic effects. Organotin and -lead compounds are known to be hi ghly neurotoxic but the molecular mechanisms by which such substances act are only poorly understood. We investigated the effects of five di fferent organometals [trimethyllead (Me3Pb+), triethyllead (Et3Pb+), t riphenyllead (Ph3Pb+), dibutyltin (But(2)Sn(2+)) and trimethyltin (Me3 Sn+)] on cytoskeletal structure as well as on cell cycle distribution and proliferation of cells in culture. Normal rat kidney cells (NRK) n ormally express so-called stress fibers of actin filaments. These fibe rs, visualized by rhodamine-phalloidin staining, were monomerized by a ll compounds in a concentration dependent manner. The influence on the cytoskeleton suggested that an alteration of cell cycle distribution and/or proliferation may be likely. However, not all tested compounds exerted an effect on these parameters. Whereas Me?Pbf and Et Pbf block ed cell division of undifferentiated HL-60 cells leading to an increas e in G(2)/mitosis, Ph3Pb+ has not such an effect. Out of the tin compo unds, only Me3Sn+ induced alterations on the cell cycle by increasing the cell number within G(1)-phase. The differences in the action of th e organometals may be due to the very low concentrations that have to be used for long-term incubations during cell cycle investigations.