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Neurotoxicology. 2012 Oct;33(5):1086-95. doi: 10.1016/j.neuro.2012.05.017. Epub 2012 Jun 9.

Differential DNA damage response to UV and hydrogen peroxide depending of differentiation stage in a neuroblastoma model.

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  • 1Depto Medicina Genomica Y Toxicologia Ambiental, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma De Mexico, Mexico D.F. C.P. 04510, Mexico.

Abstract

DNA is a frequent target of oxidative damage, and DNA damage removal is therefore a crucial process in prevention of or recovery from degenerative diseases. DNA repair is an essential system for maintaining the inherited nucleotide sequence of genomic DNA over time. Cells engage in efficient DNA repair mechanisms, the activity of which can vary depending on the type of lesion and the developmental stage. Base excision repair (BER) and nucleotide excision repair (NER) are the major repair pathways addressed in this study. BER is the principal mechanism for repair of DNA oxidative lesions, while NER is the mechanism for repair of a variety of helix-distorting lesions such as those caused by UV radiation. Recent studies suggest that NER plays a cooperative role in removal of oxidative lesions. Little is known about the roles of DNA damage sensors and repair factors in terminally differentiated, non-proliferating cells such as neurons, which are vulnerable to oxidative damage from reactive oxygen species generated by endogenous or exogenous agents. We used the human neuroblastoma MSN cell model to investigate whether terminally differentiated neuronal cells respond to lesions cause in the DNA helix, such as UV-induced CPD and the major DNA oxidative lesion 8OHdG, and thereby clarify the role of NER capacity. We observed differences in DNA damage removal depending on the challenge insult and the differentiation state. Differentiated MSN cells, compared with undifferentiated cells, showed greater sensitivity to UVC and decreased DNA damage over time. In contrast, undifferentiated cells displayed genotoxicity induced by oxidative insult and tended to accumulate DNA damage and 8OHdG lesions over time. Our findings suggest the participation of GG-NER, TC-NER and BER proteins in the removal of 8-OHG and CPDs indicating a dynamic role in overall response to damage.

Copyright © 2012 Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
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