MODIFICATION OF CELL-CYCLE AND VIABILITY OF TLX5 LYMPHOMA IN-VITRO BYSULFOXIDE-RUTHENIUM COMPOUNDS AND CISPLATIN DETECTED BY FLOW-CYTOMETRY

The effects of Na[trans-RuCl4(DMSO)Im] (NAMI), Na[trans-RuCl4(TMSO)Ind ] (TIND) and Na[trans-RuCl4(TMSO)Iq] TEQU) were tested in vitro on TLX 5 lymphoma cells in comparison to cisplatin by means of the sulforhoda mine-B test SRB) for protein content determination, by acridine orange and propidium iodide staining and by means of the bromodeoxyuridine t est: for cell cycle modifications. After Ih drug exposure with metal-b ased drugs, TLX5 lymphoma cells require a further 72 h in vitro cultiv ation to show alteration of cell cycle. Ruthenium compounds show a dif ferent pattern of effects: TEQU causes the same dose-dependent cytotox icity and DNA fragmentation shown by cisplatin, TIND reduces absorbanc e with the SRB test and slightly increases S and G(2)M populations wit h a lime-dependent drug exposure of tumour cells, and NAMI is virtuall y devoid of any detectable effect. By in vivo bioassay of in vitro tre ated tumour cells, TIND and TEQU are effective independently of the ti me of drug exposure of tumour cells, this effect being confirmed by th e same cell uptake of ruthenium after 1 or 4 h treatment, determined b y atomic absorption spectroscopy. These data stress the lack of the in volvement of direct cytotoxic effects in the potent anti-metastatic ac tion of NAMI. (C) 1998 Elsevier Science Ireland Ltd. All rights reserv ed.