Structural Alterations in the DNA of Stroma and Epithelium From the Female Breast

Published

October 12, 2021

Author(s)

Donald C. Malins, Katie M. Anderson, Pawel Jaruga, Callie R. Ramsey, Naomi K. Gilman, Virginia M. Green, Steven W. Rostad, Joanne T. Emerman, M. Dizdaroglu

Abstract

Reciprocal interactions between the stroma and epithelium are considered to be intimately associated with the development of breast cancer. In studies of whole breast tissues, a keen interest exists in the occurrence of the mutagenic DNA lesions 8-hydroxy-2'-deoxyguanosine and 8-hydroxy-2'-deoxyadenosine. However, there is an apparent lack of information on the occurrence of these lesions in the DNA of the stroma, epithelium, and myoepithelium, despite the fact that these oxidation products may significantly influence the reciprocal interactions implicated in carcinogenesis. We report age-related increases in concentrations of both lesions in the stromal DNA, which occur roughly commensurate with the known rise in breast cancer incidence between 30 and 40 years of age. However, plots of lesion concentrations revealed an uneven distribution, with some younger women having relatively high concentrations and some older women having relatively low concentrations. This finding implies that while increased age is a probable factor in lesion accumulations, other factors may also be influential [e.g., cellular concentrations of reactive oxygen species (ROS)]. Moreover, distinct differences were found between the base and backbone structures of the stromal DNA from younger women (ages 17 - 30), compared to older women (ages 50 - 62). In addition, comparisons of matched stromal, epithelial, and myoepithelial DNA (from the same individual) showed no differences between these cellular groups, suggesting a random attack by the hydroxyl radical on all three groups. Collectively, the findings reveal that the structural changes in DNA described may potentially disrupt the normal reciprocal interactions between the cell types, thus increasing breast cancer risk.

Citation

Journal of the National Cancer Institute

Pub Type

Journals

Keywords

8-Hydroxy-purinenucleosides, breast cancer, LC/MS, novel biomarkers, oxidative DNA damage

Citation

Malins, D. , Anderson, K. , Jaruga, P. , Ramsey, C. , Gilman, N. , Green, V. , Rostad, S. , Emerman, J. and Dizdaroglu, M. (2021), Structural Alterations in the DNA of Stroma and Epithelium From the Female Breast, Journal of the National Cancer Institute (Accessed April 23, 2024)