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Accumulation of Oxidatively Induced DNA Damage in Human Breast Cancer Cell Lines Following Treatment with Hydrogen Peroxide

Simon G. Nyaga, Pawel Jaruga, Althaf Lohani, Miral Dizdaroglu and Michele K. Evans

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Breast cancer is a leading cause of cancer deaths in women. Although the causes of this disease are largely unknown, inefficient repair of oxidatively induced DNA lesions has been thought to play a major role in the transformation of normal breast tissue to malignant breast tissue. Previous studies have revealed higher levels of 8-hydroxyguanine in malignant breast tissue compared to non-malignant breast tissue. Furthermore, some breast cancer cell lines have greatly reduced capacity to repair this lesion suggesting that oxidatively induced DNA lesions may be elevated in breast cancer cells. We used liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry to measure the levels of 8-hydroxy-2’-deoxyadenosine, (5’S)-8,5’-cyclo-2’-deoxyadenosine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 4,6-diamino-5-formamidopyrimidine in MCF-7 and HCC1937 breast cancer cell lines before and after exposure to H2O2 followed by a DNA repair period. We show that H2O2-treated HCC1937 and MCF-7 cell lines accumulate significantly higher levels of these lesions than the untreated cells despite a 1 h repair period. In contrast, the four lesions did not accumulate to any significant level in H2O2-treated non-malignant cell lines, AG11134 and HCC1937BL. Furthermore, MCF-7 and HCC1937 cell lines were deficient in the excision repair of all the four lesions studied. These results suggest that oxidatively induced DNA damage and its repair may be critical in the etiology of breast cancer.

Authors

Simon G. Nyaga

National Institutes of Health, Baltimore, Maryland

Pawel Jaruga

University of Maryland, Baltimore, Maryland

Althaf Lohani

National Institutes of Health, Baltimore, Maryland

Miral Dizdaroglu

National Institute of Standards and Technology, Gaithersburg, Maryland

Michele K. Evans

National Institutes of Health, Baltimore, Maryland

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.