MULTIWAVELENGTH VIDEOMICROFLUOROMETRIC STUDY OF SOME HUMAN LEUKEMIC LYMPHOBLASTS - EFFECT OF ADRIAMYCIN ON SOME BIOLOGICAL PARAMETER

The development of multidrug resistance (MDR) in heterogeneous cell se nsitive and resistant populations to a variety of clinically important cytotoxic drugs poses a major obstacle to cancer chemotherapy, The MD R phenotype is characterized by a decrease the intracellular drug accu mulation and by an overexpression of the MDR1 gene which encodes the m embrane protein, P-glycoprotein (Pgp). To evaluate the MDR phenotype, rationale investigations of the cytotoxic processes and effects of Adr iamycin (ADR) were done to obtain information on individual cells. Suc h information could be obtained through a multiparametric approach inv olving multiwavelength microfluorometry and numerical image analysis o n single living cells. To acheive this, cells should be simultaneously stained with Hoechst 33342 (nuclear staining), Rhodamine 123 (mitocho ndria staining) and Nile Red (cell cor?tour delineation). Changes in t he biological parameters accessible from R123, Ho33342 and C-SNARF-1/A M (probe used for the pHi measurements) labelling were found more info rmative than changes in morphological parameters for the discriminatio n of sensitive and resistant cells. Furthermore, this approach allows the discrimination between two resistant cell lines expressing differe nt mechanisms of resistance.