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ToxSci Advance Access originally published online on November 13, 2006
Toxicological Sciences 2007 95(2):376-382; doi:10.1093/toxsci/kfl166
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

8-Oxoguanine DNA Glycosylase and MutY Homolog Are Involved in the Incision of Arsenite-Induced DNA Adducts

Yeong-Shiau Pu*, Kun-Yan Jan{dagger}, Tsing-Cheng Wang{dagger}, Alexander S. S. Wang* and Jia-Ran Gurr{ddagger},1

* Department of Urology, National Taiwan University College of Medicine, Taipei 10002, Taiwan, ROC {dagger} Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan, ROC {ddagger} Hsing Wu College, Linkou, Taipei County 24452, Taiwan, ROC

1 To whom correspondence should be addressed at Hsing Wu College, No. 101, Section 1, Fen-Liao Road, Linkou, Taipei County 24452, Taiwan, ROC. Fax: +886-2-26010799. E-mail: 090012{at}mail.hwc.edu.tw.

Received September 15, 2006; accepted November 18, 2006


  Abstract

Since arsenite is known to induce oxidative DNA damage in human cells, we asked if it induces other types of DNA damage and how the DNA damage is repaired. Treatment of human promyelocytic leukemia NB4 cells with 0.5µM As2O3 for 30 min induced no DNA breaks, as analyzed by a standard comet assay. However, breaks were detected if these cells were then digested with endonuclease III (EnIII), formamidopyrimidine-DNA glycosylase (Fpg), or a nuclear extract (NE) of NB4 cells. Using either H2O2-Fe–treated nuclei or As2O3-treated cells, digestion with either NE or EnIII + Fpg generated the same amount of breaks, and subsequent treatment with EnIII + Fpg resulted in no increase in breaks in NE-digested cells and vice versa. The human cell lines, defective in nucleotide excision protein, such as xeroderma pigmentosum (XP) A, XPD, and XPG, excised Ultraviolet C-induced adducts less rapidly than normal fibroblasts, but excised As2O3 adducts at the same rate as the normal cells. Immunodepletion of the NE with antibody against 8-oxoguanine DNA glycosylase (OGG1) or MutY homolog (MYH) decreased the incision of As2O3-induced adducts, while antibodies against XPA, XPB, XPD, XPF, or XPG, did not. These results suggest that As2O3 induces the formation of only oxidative DNA adducts and that OGG1 and MYH are involved in this incision process.

Key Words: arsenic trioxide; oxidative damage; monomethylarsonic acid; dimethylarsinic acid; sodium arsenite.


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