A new multidrug-resistant variant (OAW42-A) of a human ovarian carcinoma line has been selected by exposure to increasing concentrations of doxorubicin. The variant is resistant to doxorubicin, vincristine (but surprisingly not to colchicine), etoposide, tenoposide and also to cisplatin (a drug not usually involved in classical multidrug resistance), but not to 5-fluorouracil. Overexpression of P-glycoprotein in the resistant line was demonstrated by immunofluorescence and western blotting. Direct evidence for P-glycoprotein as a determinant of resistance was provided by transfection with a specific antisense oligonucleotide. Reversal was incomplete and this, along with the pattern of cross-resistance observed, suggests that additional mechanisms of resistance may also be involved. Substantial clonal variation in resistance exists within the cell line.
Dublin City University ->