Effects of PEMF on a murine osteosarcoma cell line: Drug-resistant (P-glycoprotein-positive) and non-resistant cells

After pulsed exposure of Dunn osteosarcoma cells (nonresistant cells) to Ad riamycin (ADR) at increasing concentrations and single-cell cloning of surv iving cells, ADR-resistant cells were obtained. These resistant cells expre ssed P-glycoprotein and had resistance more than 10 times that of their non resistant parent cells. Compared to the nonresistant cells not exposed to p ulsing electromagnetic fields (PEMF) in ADR-free medium, their growth rates at ADR concentrations of 0.01 and 0.02 mu g/ml, which were below IC50, wer e 83.0% and 61.8%, respectively. On the other hand, in the nonresistant cel ls exposed to PEMF (repetition frequency, 10 Hz; rise time, 25 mu sec, peak magnetic field intensity, 0.4-0.8 mT), the growth rate was 111.9% in ADR-f ree medium, 95.5% at an ADR concentration of 0.01 mu g/mL, and 92.2% at an ADR concentration of 0.02 mu g/ml. This promotion of growth by PEMF is cons idered to be a result of mobilization of cells in the nonproliferative peri od of the cell cycle due to exposure to PEMF. However, at ADR concentration s above the IC50, the growth rate tended to decrease in the cells not expos ed to PEMF This may be caused by an increase in cells sensitive to ADR resu lting from mobilization of cells in the non-proliferative period to the cel l cycle. The growth rate in the resistant cells exposed to PEMF was signifi cantly lower than that in the non-exposed resistant cells at all ADR concen trations, including ADR-free culture (P less than or equal to 0.0114). Ther efore, this study suggests that PEMF promotes the growth of undifferentiate d cells but progressively suppresses the growth of more differentiated cell s, i.e., PEMF controls cell growth depending on the degree of cell differen tiation. This study also shows the potentiality of PEMF as an adjunctive tr eatment method for malignant tumors. (C) 2000 Wiley-Liss, Inc.