Novotny Nathan M, Grosfeld Jay L, Turner Katharyn E, Rescorla Frederick J, Pu Xinzhu, Klaunig James E, Hickey Robert J, Malkas Linda H, Sandoval John A
Department of Surgery, Indiana University School of Medicine and Riley Hospital for Children, Indianapolis, IN 46202, USA.
J Pediatr Surg. 2008 Feb;43(2):330-4. doi: 10.1016/j.jpedsurg.2007.10.040.
Reactive oxygen species have been shown to be initiators/promotors of tumorigenesis. Because evidence supports the role of increased oxidative stress in solid tumors, we sought to establish this relationship in neuroblastoma (NB). The aim of the study was to investigate the extent of oxidative DNA damage and antioxidative status in a progressive animal model of human NB.
Tumors were induced in the left kidneys of nude mice by the injection of cultured human NB cells (10(6)). Blood was collected from tumor-bearing mice and controls at 2, 4, and 6 weeks. Peripheral blood leukocyte oxidative DNA damage was determined using single-cell gel electrophoresis (comet assay), and plasma antioxidant capacity was assessed by the Trolox equivalent antioxidant capacity method.
Levels of oxidative DNA damage in peripheral blood leukocytes of NB-bearing mice were increased by 166%, 110%, and 87% as compared with healthy controls at 2, 4, and 6 weeks, respectively. Plasma total antioxidant values for tumor-bearing mice were not significantly different from control mice.
Our results indicate an increase of oxidative stress in an animal model of human NB, especially in the early stages of growth. Yet, we did not observe an appreciable response in plasma antioxidant activity. Because an altered redox status has been implicated in tumor maintenance and progression, these findings support the notion of a complex oxidant-antioxidant imbalance contributing to NB growth.
活性氧已被证明是肿瘤发生的引发剂/促进剂。由于有证据支持氧化应激增加在实体瘤中的作用，我们试图在神经母细胞瘤（NB）中确立这种关系。本研究的目的是在人NB的渐进性动物模型中研究氧化DNA损伤的程度和抗氧化状态。
通过注射培养的人NB细胞（10⁶）在裸鼠左肾诱导肿瘤。在第2、4和6周从荷瘤小鼠和对照小鼠采集血液。使用单细胞凝胶电泳（彗星试验）测定外周血白细胞氧化DNA损伤，并通过Trolox等效抗氧化能力法评估血浆抗氧化能力。
与健康对照相比，荷瘤小鼠外周血白细胞中氧化DNA损伤水平在第2、4和6周分别增加了166%、110%和87%。荷瘤小鼠的血浆总抗氧化值与对照小鼠无显著差异。
我们的结果表明人NB动物模型中氧化应激增加，尤其是在生长早期。然而，我们未观察到血浆抗氧化活性有明显反应。由于氧化还原状态改变与肿瘤维持和进展有关，这些发现支持了复杂的氧化剂-抗氧化剂失衡促成NB生长这一观点。
