INDUCTION OF P-GLYCOPROTEIN FUNCTIONAL-ACTIVITY AND MULTIDRUG-RESISTANCE BY A SOLUBLE FACTOR(S) PRODUCED BY SOME MAMMALIAN-CELLS

In the previous study we have found that Djungarian hamster fibroblast s with the high level of multidrug resistance (MDR) (colchicine-resist ance index RI of 1000 to 42000) produce soluble factor(s) communicatin g MDR to the drug-sensitive cells of the same species by elevating P-g lycoprotein (Pgp) functional activity. Here we have shown that these c ells can influence in the same fashion human tumour cells. Rat hepatom a McA RH7777 cells and their colchicine-resistant derivatives are show n to produce a factor with similar effects (induction of MDR and Pgp f unctional activity in the drug-sensitive cells). These effects seem to depend on the drug resistance level. Our results show that induction of the Pgp-mediated MDR is not species-specific and that tumour cells with intrinsic MDR (arising from the tissue with a high level of Pgp e xpression) can produce a factor(s) communicating this type of drug res istance to the sensitive cells.