Oxidative status in neuroblastoma: a source of stress?

Abstract

Aim of Study-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.Methods-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.Main Results-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.Conclusions-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. By describing the oxidation status in the circulation of a well-established NB mouse model, we hope to gain insight into the host oxidative response to tumor burden. Past work evaluating tumor growth has concentrated on studying how cancer cell growth adapts and modulates to hypoxic conditions [4][5][6]. Because oxygen deficiency elevates the expression of reactive oxygen species (ROS) production, antioxidants are generated within the cell to defend against excess ROS production. By analyzing how the host responds to tumor challenge, ramifications of this work include improved understanding of the oxidative microenvironment surrounding NB growth and potentially lead to the design of new therapeutic strategies based on a child's redox status. Index words Materials and methods NB athymic mouse modelThe human NB cell line, SK-N-AS, was grown as a monolayer in Dulbecco's modified Eagle's medium with 4 mmol/L L-glutamine adjusted to contain 1.5 g/L sodium bicarbonate, 4.5 g/L glucose, and 10% fetal bovine serum at 37°C in 5% CO 2 . Cells were harvested, counted (10 6 ), and prepared as previously described [7]. A total of 29 NCR female nude mice (4-6 weeks old) were used. After a 7-day acclimation period, mice were separated into 4 groups; group 1 (control, n = 6), group 2 (2-week tumor, n = 7), group 3 (4-week tumor, n = 7), and group 4 (6-week tumor, n = 7). Controls for each experimental group underwent a sham operation, and the left kidneys were injected (100 μL) with phosphate-buffered saline. Mice were anesthetized an...

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