Effects of doxorubicin on human dental pulp cells in vitro

There is substantial information concerning the effects of continuous exposure to supratherapeutic or therapeutic concentrations of doxorubicin on human molar pulpal cells; the effects of continuous exposure to subtherapeutic concentrations of this agent are undetermined. To this end, we studied the proliferation of human fibroblasts and pulpal cells and their pattern of mineralized nodule deposition in vitro. Cell proliferation was assessed at 1, 3, 5, and 7 days from populations with either no exposure (control) or exposure to 10(-6)-10(-9) mol/L doxorubicin. Mineralized nodule deposition and calcium-45 incorporation were assessed at 7 and 21 days of culture. Data were compared by factorial ANOVA and a post-hoc Tukey test. 10(-6) and 10(-7) mol/L doxorubicin significantly reduced the total number of viable pulpal cells in cultures from days 1 to 3 (p < 0.05); doxorubicin 10(-6)-10(-9) mol/L significantly inhibited cell proliferation (p < 0.05) and DNA synthesis 5 days after plating (p < 0.001). After 21 days, doxorubicin 10(-6)-10(-8) mol/L significantly decreased calcium-45 incorporation into pulpal cultures (p < 0.001); all dilutions significantly reduced the number of mineralized nodules within the 21-day pulpal cultures (p < 0.05). In addition, all dilutions of doxorubicin significantly inhibited fibroblast cell proliferation and incorporation of [(3)H]thymidine. In contrast, the fibroblast cultures did not produce mineralized nodules, suggesting that the mineralized nodules within the pulpal cell cultures did not result from dystrophic calcification. Thus, exposure to subtheraputic doxorubicin concentrations has potential adverse effects on mineralized tissue formation within the pulp, which could affect the rates of reparative dentin deposition within the tooth pulps of patients receiving this chemotherapeutic agent.