Oxidative status in neuroblastoma: a source of stress?
OBJECTIVE
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.


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.
Novotny
Nathan M
NM
Department of Surgery, Indiana University School of Medicine and Riley Hospital for Children, Indianapolis, IN 46202, USA. nmnovotn@iupui.edu
Grosfeld
Jay L
JL
Turner
Katharyn E
KE
Rescorla
Frederick J
FJ
Pu
Xinzhu
X
Klaunig
James E
JE
Hickey
Robert J
RJ
Malkas
Linda H
LH
Sandoval
John A
JA
D000818:Animals; D000831:Animals, Newborn; D020552:Comet Assay; D004249:DNA Damage; D004195:Disease Models, Animal; D004586:Electrophoresis; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology*; D011336:Probability; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D017382:Reactive Oxygen Species