8-hydroxyguanosine and Neuroblastoma

Neuroblastomas are childhood tumors with frequent fatal relapses after induction treatment, which is related to tumor evolution with additional genomic events. Our whole-genome sequencing data analysis revealed a high frequency of somatic cytosine > adenine (C > A) substitutions in primary neuroblastoma tumors, which was associated with poor survival. We showed that increased levels of C > A substitutions correlate with copy number loss (CNL) of

Topics: Adenine; Child; Cytosine; DNA Damage; DNA Glycosylases; DNA Repair; Female; Guanine; Guanosine; Humans; Male; Mutagenesis; Neoplasm Recurrence, Local; Neuroblastoma; Oxidative Stress; Polymorphism, Single Nucleotide

Alzheimer's disease (AD) is the leading cause of dementia in developed countries. It is characterized by two major pathological hallmarks, one of which is the extracellular aggregation of the neurotoxic peptide amyloid-β (Aβ), which is known to generate oxidative stress. In this study, we showed that the presence of Aβ in a neuroblastoma cell line led to an increase in both nuclear and mitochondrial DNA damage. Unexpectedly, a concomitant decrease in basal level of base excision repair, a major route for repairing oxidative DNA damage, was observed at the levels of both gene expression and protein activity. Moreover, the addition of copper sulfate or hydrogen peroxide, used to mimic the oxidative stress observed in AD-affected brains, potentiates Aβ-mediated perturbation of DNA damage/repair systems in the "Aβ cell line". Taken together, these findings indicate that Aβ could act as double-edged sword by both increasing oxidative nuclear/mitochondrial damage and preventing its repair. The synergistic effects of increased ROS production, accumulated DNA damage and impaired DNA repair could participate in, and partly explain, the massive loss of neurons observed in Alzheimer's disease since both oxidative stress and DNA damage can trigger apoptosis.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Cell Line, Tumor; DNA Damage; DNA Repair; DNA, Mitochondrial; Gene Expression; Gene Expression Regulation, Neoplastic; Guanosine; Humans; Neuroblastoma; Oxidants; Oxidative Stress; Peptide Fragments