Unaltered expression of multidrug resistance transporters in polycyclic aromatic hydrocarbon-resistant rat liver cells

Rat liver epithelial cells resistant to the chemical carcinogen 3MC, termed F258/3MC cells and generated by long-term exposure of parental F258 cells to the PAH, were characterized, especially with respect to expression of mu ltidrug resistance transporters: such as P-glycoprotein, MRP1 and MRP2. F25 8/3MC cells were found to be cross-resistant to other PAHs such as BP and d imethylbenzl(a)anthracene but remained sensitive to known substrates of mul tidrug resistance efflux pumps such as doxorubicin and vincristine. They di d not display either decreased cellular PAH accumulation or increased PAH e fflux. In addition, P-glycoprotein and MRP2 mRNA levels were not, or only b arely detected, in F358/3MC cells and in their parental counterparts wherea s these PAM-resistant and sensitive cells showed closed levels of MRP1 mRNA s and activity. Moreover, P-gp- and MRP1-overexpressing cells were shown to display similar accumulation and efflux of BP than those Found in P-gp- an d MRP1-negative control cells. These data therefore suggest that multidrug resistance transporters do not contribute to PAH resistance in PAH-selected liver cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.