Effect of methotrexate doxorubicin and mitoxantrone on human peritoneal mesothelial cell function in vitro

Recent studies have demonstrated that intraperitoneal instillation of dialysis solutions and drug additives may adversely affect the function of peritoneal cell populations. Therefore the aim of the present investigation was to examine the short-term effects of antineoplastic agents on human peritoneal mesothelial cells (HPMC). We have assessed the integrity of HPMC membrane and mechanisms of intracellular potassium transport. There was no evidence of significant cytotoxicity (as measured by ⁸⁶Rb release) during a 60-min exposure of HPMC to either methotrexate (10^-6-10^-4M), doxorubicin (10^-7-10^-5 M) or mitoxantrone (10^-7-10^-5 M). In HPMC exposed to doxorubicin (10^-6 M) the intracellular transport of potassium, as assessed with ⁸⁶Rb as its analogue, was not affected. Methotrexate (10^-5 M) diminished Na,K-ATPase activity and simultaneously enhanced the ⁸⁶Rb transport via furosemide-sensitive pathway. Mitoxantrone reduced the furosemide-sensitive ⁸⁶Rb influx in a dose-dependent manner and at a concentration of 10^-4 M it also impaired the ouabain-dependent ⁸⁶Rb influx. These data demonstrate that antineoplastic agents interfere with HPMC function which might contribute to the oncostatic-induced peritoneal toxicity.