Pant M C, Liao X-Y, Lu Q, Molloi S, Elmore E, Redpath J L
Department of Radiation Oncology, University of California Irvine, Irvine, CA 92697, USA.
Carcinogenesis. 2003 Dec;24(12):1961-5. doi: 10.1093/carcin/bgg172. Epub 2003 Sep 26.
Suppression of neoplastic transformation of HeLa x skin fibroblast human hybrid cells in vitro following low doses of low linear energy transfer radiation has been reported previously. The present study represents an exploration of two hypothesized mechanisms that may underlie this observed suppression. These are the up-regulation of reduced glutathione (GSH), a known antioxidant, and induction of DNA repair activity. The hybrid cells were found to have a high endogenous level of GSH and no induction following low doses of 60 kVp X-rays was observed. Buthionine sulfoximine (BSO), a GSH biosynthesis inhibitor, completely suppressed GSH levels in both unirradiated and irradiated cells. Furthermore, there was no significant impact of BSO-induced suppression of GSH on the neoplastic transformation frequency of either unirradiated or low dose irradiated cells indicating that glutathione levels play no role in the low dose suppression of transformation frequency. To assess the possible role of DNA repair in the low dose suppression of transformation the effect of 3-aminobenzamide (3-AB), a poly-ADP-ribose polymerase (PARP) inhibitor was examined. In these experiments, there was no significant effect of 3-AB on the transformation frequency at a dose of Cs-137 gamma rays of 0.5 cGy, however, at a dose of 5 cGy there was a significant increase (P < 0.05) in the transformation frequency in the presence of 3-AB. These findings suggest that the influence of DNA repair on the low dose suppression of transformation is significant at a dose of 5 cGy, but not at the lower dose of 0.5 cGy.
先前已有报道称，低剂量低线性能量转移辐射可抑制体外培养的HeLa细胞与皮肤成纤维细胞杂交的人杂交细胞的肿瘤转化。本研究旨在探索可能导致这种观察到的抑制现象的两种假设机制。这两种机制分别是已知抗氧化剂还原型谷胱甘肽（GSH）的上调以及DNA修复活性的诱导。研究发现杂交细胞内源性GSH水平较高，且低剂量60 kVp X射线照射后未观察到诱导现象。丁硫氨酸亚砜胺（BSO）是一种GSH生物合成抑制剂，可完全抑制未照射和照射细胞中的GSH水平。此外，BSO诱导的GSH抑制对未照射或低剂量照射细胞的肿瘤转化频率均无显著影响，这表明谷胱甘肽水平在低剂量抑制转化频率中不起作用。为了评估DNA修复在低剂量抑制转化中的可能作用，研究了聚ADP核糖聚合酶（PARP）抑制剂3-氨基苯甲酰胺（3-AB）的作用。在这些实验中，在Cs-137γ射线剂量为0.5 cGy时，3-AB对转化频率无显著影响，然而，在剂量为5 cGy时，在存在3-AB的情况下转化频率显著增加（P < 0.05）。这些发现表明，DNA修复对低剂量抑制转化的影响在剂量为5 cGy时显著，但在较低剂量0.5 cGy时不显著。
