Department of Pharmacology, Chung Shan Medical University Department of Dentistry, Taiwan.
Int Endod J. 2012 Jun;45(6):499-507. doi: 10.1111/j.1365-2591.2011.02001.x. Epub 2012 Jan 14.
To evaluate the potential toxicological implications of BisGMA on murine macrophage cell line RAW264.7.
Lactate dehydrogenase release, flow cytometry, Western blot and fluorometric assays were used to detect cell viability, mode of cell death and caspase activities, respectively. In addition, alkaline single-cell gel electrophoresis and cytokinesis-block micronucleus assays were applied to detect genotoxicity. Statistical analyses were performed using anova followed by the Bonferroni's t-test for multi-group comparisons test.
BisGMA demonstrated a cytotoxic effect on RAW264.7 cells in a dose-dependent and a time-dependent manner (P < 0.05). BisGMA was found to induce two modes of cell death. The mode of cell death changed from apoptosis to necrosis as the concentrations of BisGMA elevated. Caspase-3, caspase-8 and caspase-9 activities were significantly induced by BisGMA in a dose-dependent manner (P < 0.05). Moreover, BisGMA exhibited genotoxicity via a dose-related increase in the numbers of micronucleus and DNA strand breaks (P < 0.05).
Cytotoxicity and genotoxicity induced by BisGMA are mediated by DNA damage and caspase activation.
评估 BisGMA 对小鼠巨噬细胞 RAW264.7 细胞的潜在毒理学影响。
采用乳酸脱氢酶释放、流式细胞术、Western blot 和荧光测定法分别检测细胞活力、细胞死亡方式和半胱天冬酶活性。此外，应用碱性单细胞凝胶电泳和胞质分裂阻断微核试验检测遗传毒性。采用方差分析，并用 Bonferroni t 检验进行多组比较检验进行统计分析。
BisGMA 呈剂量依赖性和时间依赖性方式对 RAW264.7 细胞产生细胞毒性作用（P<0.05）。BisGMA 诱导两种细胞死亡方式。随着 BisGMA 浓度的升高，细胞死亡方式由凋亡转变为坏死。BisGMA 呈剂量依赖性显著诱导半胱天冬酶-3、半胱天冬酶-8 和半胱天冬酶-9 活性（P<0.05）。此外，BisGMA 通过增加微核和 DNA 链断裂的数量呈现出与剂量相关的遗传毒性（P<0.05）。
BisGMA 诱导的细胞毒性和遗传毒性是通过 DNA 损伤和半胱天冬酶激活介导的。
