Progression of human breast cancers to the metastatic state is linked to hydroxyl radical-induced DNA damage.
Hydroxyl radical damage in metastatic tumor DNA was elucidated in women with breast cancer, and a comparison was made with nonmetastatic tumor DNA. The damage was identified by using statistical models of modified base and Fourier transform-infrared spectral data. The modified base models revealed a greater than 2-fold increase in hydroxyl radical damage in the metastatic tumor DNA compared with the nonmetastatic tumor DNA. The metastatic tumor DNA also exhibited substantially greater base diversity than the nonmetastatic DNA, and a progression of radical-induced base damage was found to be associated with the growth of metastatic tumors. A three-dimensional plot of principal components from factor analysis, derived from infrared spectral data, also showed that the metastatic tumor DNA was substantially more diverse than the tightly grouped nonmetastatic tumor DNA. These cohesive, independently derived findings suggest that the hydroxyl radical generates DNA phenotypes with various metastatic potentials that likely contribute to the diverse physiological properties and heterogeneity characteristic of metastatic cell populations.
Malins
D C
DC
Molecular Epidemiology Program, Pacific Northwest Research Foundation, Seattle, Washington 98122, USA.
Polissar
N L
NL
Gunselman
S J
SJ
D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D004967:Estrogens / Q000737:chemistry; D005260:Female; D006801:Humans; D017665:Hydroxyl Radical / Q000633:toxicity*; D008207:Lymphatic Metastasis; D013058:Mass Spectrometry; D009362:Neoplasm Metastasis; D010084:Oxidation-Reduction; D013055:Spectrophotometry, Infrared
D004273:DNA, Neoplasm; D004967:Estrogens; D017665:Hydroxyl Radical