The multidrug resistance (MDR) is one of the main reasons for chemotherapeu
tic failures in cancer patients, The overexpression of an MDR1 gene product
, P-glycoprotein (Pgp), leads to the appearance of resistant tumor cells, I
n the previous paper(Erokhina, 1997) we demonstrated that the first stages
of the Pep-mediated MDR are accompanied by the reorganization of cytoskelet
on elements and the vacuolar system. These data were true for two independe
ntly isolated sublines of Syrian hamster embryo fibroblasts transformed by
the Raus sarcoma virus, In this study we continued the investigation of pro
perties of the vacuolar system in Pgp-expressing cells. Brefeldin A (BFA),
which is not a Pgp substrate, affects different elements of vacuolar system
and blocks vesicular transport, Our data demonstrate that BFA has differen
t effects on parental and resistant cells, In parental-cells, the Golgi app
aratus and vesicular transport are sensitive to BFA, while in resistant sub
lines, BFA affects the vesicular transport, but not the Golgi apparatus str
ucture. We discuss the existance of similar and different BFA targets in pa
rental and resistant cells and their role in the evolution of multidrug res
istant mechanisms.