Oxidative changes in the DNA of stroma and epithelium from the female breast: potential implications for breast cancer.
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 presence of these lesions in the DNA of the stroma, epithelium, and myoepithelium, despite the fact that these oxidation products may significantly influence reciprocal interactions between these cell types 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, no further increases in these concentrations occurred in the older women. 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)]. 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 in DNA damage, suggesting a random attack by the hydroxyl radical on all three groups. Collectively, the findings imply that the structural changes in DNA described may potentially disrupt normal reciprocal interactions between the cell types, thus increasing breast cancer risk.
Malins
Donald C
DC
Biochemical Oncology Program, Pacific Northwest Research Institute, Seattle, Washington 98122, USA. dcmalins@dcmalins.com
Anderson
Katie M
KM
Jaruga
Pawel
P
Ramsey
Callie R
CR
Gilman
Naomi K
NK
Green
Virginia M
VM
Rostad
Steven W
SW
Emerman
Joanne T
JT
Dizdaroglu
Miral
M
D000293:Adolescent; D000328:Adult; D001940:Breast / Q000166:cytology* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology*; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress; D017154:Stromal Cells / Q000378:metabolism*
D004247:DNA; D003849:Deoxyguanosine