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[Cancer Research 58, 222-225, January 15, 1998]
© 1998 American Association for Cancer Research
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Highly Sensitive Apurinic/Apyrimidinic Site Assay Can Detect Spontaneous and Chemically Induced Depurination under Physiological Conditions1

Jun Nakamura, Vernon E. Walker2, Patricia B. Upton, Su-Yin Chiang, Yoke W. Kow3 and James A. Swenberg4

Department of Environmental Sciences and Engineering, The University of North Carolina, Chapel Hill, North Carolina 27599 [J. N., V. E. W., P. B. U., S-Y. C., J. A. S.], and Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont 05405 [Y. W. K.]

One of the most prevalent lesions in DNA is the apurinic/apyrimidinic (AP) site, which is derived from the cleavage of the N-glycosyl bond by DNA glycosylase or by spontaneous depurination. AP sites are repaired by AP endonucleases during the process of base excision repair; however, an imbalance in this DNA repair system may cause mutations as well as cell death. We have established a sensitive and convenient slot-blot method to detect AP sites in genomic DNA using a novel aldehyde reactive probe (ARP), which reacts with the aldehydic group of ring-opened AP sites. The reaction of 1 mM of ARP with 15 µg of genomic DNA containing AP sites at 37°C was completed within 1 min. The AP site-ARP complex was remarkably stable during incubation in TE buffer, even at 100°C for 60 min. The sensitivity of this assay enables detection of 2.4 AP sites per 107 bases. By using this ARP-slot-blot assay, the rate of spontaneous depurination of calf thymus DNA was determined. Under physiological conditions, AP sites were increased at 1.54 AP sites/106 nucleotides/day (9000 AP sites/cell/day). This highly sensitive assay allows us to determine the endogenous level of AP sites in genomic DNA, as well as to investigate whether DNA-damaging agents cause imbalances of base excision/AP endonuclease repair in vivo and in vitro.

1 Funded in part by Grant P42-ES05948 from NIEHS Superfund Basic Research Program and a grant from the Chemical Manufacturers Association.

2 Present address: New York State Department of Health, Wadsworth Center for Laboratories and Research, Empire State Plaza, P. O. Box 509, Albany, NY 12201-0509.

3 Present address: Division of Cancer Biology, Department of Radiation Oncology, Emory University School of Medicine, 145 Edgewood Ave., Atlanta, GA 30335.

4 To whom requests for reprints should be addressed, at Department of Environmental Sciences and Engineering, The University of North Carolina, CB# 7400, Chapel Hill, NC 27599-7400.

Received 9/15/97. Accepted 12/ 1/97.




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