Gaikwad Nilesh W, Yang Li, Muti Paola, Meza Jane L, Pruthi Sandhya, Ingle James N, Rogan Eleanor G, Cavalieri Ercole L
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Int J Cancer. 2008 May 1;122(9):1949-57. doi: 10.1002/ijc.23329.
Estrogens can become endogenous carcinogens via formation of catechol estrogen quinones, which react with DNA to form specific depurinating estrogen-DNA adducts. The mutations resulting from these adducts can lead to cell transformation and the initiation of breast cancer. Estrogen metabolites, conjugates and depurinating DNA adducts in urine samples from 46 healthy control women, 12 high-risk women and 17 women with breast cancer were analyzed. The estrogen metabolites, conjugates and depurinating DNA adducts were identified and quantified by using ultraperformance liquid chromatography/tandem mass spectrometry. The levels of the ratios of depurinating DNA adducts to their respective estrogen metabolites and conjugates were significantly higher in high-risk women (p < 0.001) and women with breast cancer (p < 0.001) than in control subjects. The high-risk and breast cancer groups were not significantly different (p = 0.62). After adjusting for patient characteristics, these ratios were still significantly associated with health status. Thus, the depurinating estrogen-DNA adducts are possible biomarkers for early detection of breast cancer risk and response to preventive treatment.
雌激素可通过形成儿茶酚雌激素醌而成为内源性致癌物，儿茶酚雌激素醌会与DNA反应形成特定的脱嘌呤雌激素 - DNA加合物。这些加合物导致的突变可引发细胞转化并启动乳腺癌。分析了46名健康对照女性、12名高危女性和17名乳腺癌女性尿液样本中的雌激素代谢物、结合物和脱嘌呤DNA加合物。使用超高效液相色谱/串联质谱法对雌激素代谢物、结合物和脱嘌呤DNA加合物进行鉴定和定量。高危女性（p < 0.001）和乳腺癌女性（p < 0.001）中，脱嘌呤DNA加合物与其各自雌激素代谢物和结合物的比率水平显著高于对照受试者。高危组和乳腺癌组之间无显著差异（p = 0.62）。在调整患者特征后，这些比率仍与健康状况显著相关。因此，脱嘌呤雌激素 - DNA加合物可能是早期检测乳腺癌风险和预防治疗反应的生物标志物。
