Paclitaxel restores radiation-induced apoptosis in a bcl-2-expressing, radiation-resistant lymphoma cell line

Purpose: To restore radiation-induced apoptosis in a bcl-2-expressing, radi ation-resistant murine lymphoma cell line (LY-ar) by pretreatment with pacl itaxel (Taxol), Because this cell line also has high intracellular levels o f glutathione (GSH), reportedly due to the bcl-2 expression and involved in the cell's antioxidant functions, paclitaxel treatment was correlated with GSH levels, Methods and Materials: LY-ar cells were pretreated with paclitaxel and then irradiated with 5 Gy. Apoptosis was measured by DNA fragmentation 6 h late r. Dose response and time course experiments were performed. Intracellular GSH levels were measured after treatment. Cell survival analysis was perfor med for various paclitaxel concentrations +/- 5 Gy, Results: LY-ar cells pretreated with 0 nM, 10 nM, 25 nM, and 50 nM paclitax el for 20 h underwent apoptosis at 2%, 15%, 25%, and 22%, respectively. Wit h the addition of 5-Gy irradiation, LY-ar cell apoptosis increased to 4%, 3 0%, 49%, and 57%. Maximal apoptosis was detected with a paclitaxel pretreat ment time of 20 h, Intracellular GSH levels were reduced by nearly 50% with paclitaxel pretreatment, Surviving fractions (SFs) with 0 nM, 10 nM, 25 nM , and 50 nM paclitaxel and 0 Gy were 1.0, 0.50, 0.08, and 0.05, respectivel y. SFs with 0 nM, 10 nM, 25 nM, and 50 nM paclitaxel and 5 Gy were 0.009, 0 .003, 3 x 10(-5), and 1 x 10(-5), respectively. Conclusion: Radiation-induced apoptosis in LY-ar cells was restored by pret reatment with paclitaxel. This correlated with lowered levels of intracellu lar GSH, Cell survival analysis indicated that the combination of Taxol and radiation on cell killing was greater than additive. (C) 2001 Elsevier Sci ence Inc.