Involvement of Preferential Formation of Apurinic/Apyrimidinic Sites in Dimethylarsenic-Induced DNA Strand Breaks and DNA-Protein Crosslinks in Cultured Alveolar Epithelial Cells

doi:10.1006/bbrc.1995.1179

Biochemical and Biophysical Research Communications

Volume 207, Issue 1, 6 February 1995, Pages 244-249

https://doi.org/10.1006/bbrc.1995.1179 Get rights and content

Abstract

We previously found that lung-specific DNA damage induced by administration of dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, in mice might be due to dimethylarsenic peroxyl radical [(CH₃)₂AsOO·] produced in the further metabolic processing of DMAA. Further analysis of DNA damage was performed in the present study using a human embryonic cell line of alveolar epithelial (L-132) cells. Alkali-labile sites in DNA were produced prior to DNA single-strand breaks (SSB) and DNA-protein crosslinks (PC) in L-132 cells by exposure to 10mM DMAA. An experiment using methoxyamine (MA), an agent reacting with the aldehyde group of apurinic/apyrimidinic (AP) sites in DNA, indicated that, of the alkali-labile sites formed by exposure to DMAA, major ones were AP sites. These findings suggest that SSB and PC induced by exposure of L-132 cells to DMAA occurred via the formation of AP sites in DNA. That is, SSB were produced by a β-elimination reaction on AP sites in the DNA and PC by a Schiff-base reaction between amino groups of nuclear proteins and aldehyde groups of AP sites.

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Arsenic metabolism also produces additional reactive intermediates. For example, the dimethylarsenic peroxyl radical, which is formed in the metabolism of dimethylarsenic acid, a methylated form of inorganic arsenic, further requires antioxidant remediation, and this intermediate has been shown to induce DNA damage (Flora, Bhadauria, Kannan, & Singh, 2007; Yamanaka, Hayashi, Kato, Hasegawa, & Okada, 1995). Specific forms of arsenic and their effects on oxidative stress are discussed in Section 4.
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Regular ArticleInvolvement of Preferential Formation of Apurinic/Apyrimidinic Sites in Dimethylarsenic-Induced DNA Strand Breaks and DNA-Protein Crosslinks in Cultured Alveolar Epithelial Cells

Abstract

Regular Article
Involvement of Preferential Formation of Apurinic/Apyrimidinic Sites in Dimethylarsenic-Induced DNA Strand Breaks and DNA-Protein Crosslinks in Cultured Alveolar Epithelial Cells