Evidence of difference between cytotoxicity, cell cycle and morphonuclear effects of polyamines on sensitive and multidrug resistant P388 cell lines.

This paper reports studies on the influence of multidrug resistance (MDR) on the mechanism of polyamine toxicity. The effects of putrescine (PUT), spermidine (SPD) and spermine (SPM) on morphonuclear parameters and cell cycle were studied by means of digital cell image analysis. This reveals that only SPD and SPM condense chromatin inducing a strong decrease in the nuclear area and a cell-cycle arrest in phase G2 in P388/s and the two MDR sublines. A significant difference was observed between the sensitivity of the two phenotypes, which confirms results obtained by means of a microculture tetrazolium test which showed that SPD and SPM were highly, but very differently, cytotoxic on sensitive and MDR sublines, unlike PUT, which was not toxic. This encourages us to study more thoroughly possible differences in polyamine metabolic enzymes and uptake in these cells, to enable us to acquire a better understanding of the impact of MDR phenotype on the polyamine pathway.