Journal Article

Generation of DNA base modification following treatment of cultured murine keratinocytes with benzoyI peroxide

Jeffrey K. King, Patricia A. Egner and Thomas W. Kensler

in Carcinogenesis

Volume 17, issue 2, pages 317-320
Published in print February 1996 | ISSN: 0143-3334
Published online February 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.2.317
Generation of DNA base modification following treatment of cultured murine keratinocytes with benzoyI peroxide

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BenzoyI peroxide (BzPO) is a free radical generating compound that acts as a tumor promoter and progressor in mouse skin. BzPO is cleaved in the presence of copper to produce benzoyloxyI and phenyI radicals. Treatment of mutation reporter plasmids with BzPO and copper yields predominantly single-strand breaks and G↑T transversion mutations. To explore the role of base modifications in the possible mammalian mutagenicity of BzPO the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) within the DNA of cultured murine keratinocytes was investigated. Treatment with 10 μM BzPO produced a maximum 3-fold increase in levels of 8-OHdG versus vehicle controls within1-2 h, with significant levels of 8-OHdG persisting 6 h after initial exposure to BzPO. Pretreatment with the copper chelator bathocuproine disulfonic acid reduced the levelsof 8-OHdG generated by BzOP ot near background. However, treatment with the iron chelator desferal did not. The stable metabolic product of BzPO benzoic acid was ineffective in producing 8-OHdG. Depletion of cellular glutathione with L-buthionine-(S,R)-sulfoximine increased the amount of BzPO-generated 8-OHdG, while supplementation with glutathione monoethyI ester reduced the number of 8-OHdG molecules formed. Collectively, these results suggest that BzPO at non-cytotoxic concentrations undergoes copper-dependent activation to a reactive product to generate 8-OHdG within cultured murinekeratinocytes.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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