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Title: Oxidative damage induced genotoxic effects in human fibroblasts from Xeroderma Pigmentosum group A patients
Authors: Low, G.K.M.
Fok, E.D.Z.
Ting, A.P.L.
Hande, M.P. 
Keywords: Genome instability
Nucleotide excision repair
Oxidative DNA damage
Xeroderma Pigmentosum A
Issue Date: 2008
Citation: Low, G.K.M., Fok, E.D.Z., Ting, A.P.L., Hande, M.P. (2008). Oxidative damage induced genotoxic effects in human fibroblasts from Xeroderma Pigmentosum group A patients. International Journal of Biochemistry and Cell Biology 40 (11) : 2583-2595. ScholarBank@NUS Repository.
Abstract: Xeroderma Pigmentosum A protein plays a pivotal role in the nucleotide excision repair pathway. Through site-directed binding of rigidly kinked double-stranded DNA, it verifies damaged DNA for subsequent excision and incision. Although Xeroderma Pigmentosum A-deficient cells have shown to be defective in oxidative base-lesion repair, the effects of oxidative assault on such cells have not been fully explored. Therefore, we sought to determine the involvement of Xeroderma Pigmentosum A in oxidative DNA damage-repair by treating primary fibroblasts from a patient suffering from Xeroderma Pigmentosum A with sodium arsenite and hydrogen peroxide. Our results show dose-dependent increase in genotoxicity with little change in cytotoxicity with both arsenite and H2O2 in Xeroderma Pigmentosum A-deficient cells compared to control cells. Xeroderma Pigmentosum A-deficient cells displayed increased susceptibility and reduced repair capacity when subjected to DNA damage induced by oxidative stress. Superarray results of apoptotic genes revealed differential expression of ∼10 genes between Xeroderma Pigmentosum A-deficient and normal cells following arsenite treatment. Interestingly, we noted that arsenite did not inflict as much damage in the cells compared to H2O2. Lack of functional Xeroderma Pigmentosum A seems to increase the susceptibility of oxidative stress-induced genotoxicity while retaining cell viability posing as a potential cancer risk factor of Xeroderma Pigmentosum A patients. © 2008 Elsevier Ltd. All rights reserved.
Source Title: International Journal of Biochemistry and Cell Biology
ISSN: 13572725
DOI: 10.1016/j.biocel.2008.05.009
Appears in Collections:Staff Publications

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