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首页> 美国卫生研究院文献>Cancer Biology Therapy >Infrared microspectroscopy identifies biomolecular changes associated with chronic oxidative stress in mammary epithelium and stroma of breast tissues from healthy young women
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Infrared microspectroscopy identifies biomolecular changes associated with chronic oxidative stress in mammary epithelium and stroma of breast tissues from healthy young women

机译：红外显微技术可确定与健康年轻女性的乳腺上皮和乳腺基质中的慢性氧化应激相关的生物分子变化

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Studies of the decades-long latent stages of breast carcinogenesis have been limited to when hyperplastic lesions are already present. Investigations of earlier stages of breast cancer (BC) latency have been stymied by the lack of fiducial biomarkers needed to identify where in histologically normal tissues progression toward a BC might be taking place. Recent evidence suggests that a marker of chronic oxidative stress (OxS), protein adducts of 4-hydroxy-2-nonenal (4HNE), can meet this need. Specifically: (1) 4HNE immunopositive (4HNE+) mammary epithelial (ME) cells were found to be prevalent in normal (reduction mammoplasty) tissues of most women (including many teenagers) studied, representative of those living in the United States’ high risk-posing environment and: (2) marked (>1.5-fold) differences were identified between tissues of healthy young women with many vs. few 4HNE+ ME cells in the relative levels of transcripts for 42 of the 84 OxS-associated genes represented in SABioscience Oxidative-Stress/Oxidative-Defense PCR array. Herein we used synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to identify molecular changes associated with 4HNE adducts in basal and luminal ME cells in terminal ductal units (TDLU), which are the cells of origin of BC, and associated intralobular and interlobular stroma, known contributors to carcinogenesis. Multivariate analysis-derived wavenumbers differentiated 4HNE+ and 4HNE− cells in each of the anatomical compartments. Specifically, principal component and linear discriminant analyses of mid-infrared spectra obtained from these cells revealed unambiguous, statistically highly significant differences in the “biochemical fingerprint” of 4HNE+ vs. 4HNE− luminal and basal ME cells, as well as between associated intralobular and interlobular stroma. These findings demonstrate further SR-FTIR microspectroscopy’s ability to identify molecular changes associated with altered physiological and/or pathophysiological states, in this case with a state of chronic OxS that provides a pro-carcinogenic microenvironment.
机译：乳腺癌致癌的数十年潜伏期的研究仅限于增生性病变已经存在的时候。缺乏确定在组织学上正常组织中可能发生向BC进行进展的基准生物标志物，阻碍了乳腺癌（BC）潜伏期早期的研究。最近的证据表明，慢性氧化应激（OxS）的标记物，即4-羟基-2-壬烯醛（4HNE）的蛋白质加合物，可以满足这一需求。具体来说：（1）在大多数研究的女性（包括许多青少年）的正常（复位乳房成形术）组织中，发现4HNE免疫阳性（4HNE +）乳腺上皮（ME）细胞普遍存在，代表了生活在美国高危人群中姿势环境和：（2）在具有4HNE + ME细胞的健康年轻女性组织之间，在SABioscience Oxidative所代表的84种与OxS相关的基因中，有42种的相对转录本相对水平之间存在明显差异（> 1.5倍） -胁迫/氧化防御PCR阵列。本文中，我们使用基于同步加速器辐射的傅立叶变换红外（SR-FTIR）显微光谱技术来鉴定与末梢导管单位（TDLU）的基础和管腔ME细胞中4HNE加合物相关的分子变化，TDLU是BC的起源细胞，并且与小叶内和小叶间基质，已知致癌因素。多元分析得出的波数在每个解剖室中区分了4HNE +和4HNE-细胞。具体而言，从这些细胞获得的中红外光谱的主成分和线性判别分析显示，在4HNE +与4HNE-腔和基底ME细胞的“生化指纹”以及相关的小叶内和小叶间之间的“统计生化”差异无统计学意义。基质。这些发现进一步证明了SR-FTIR显微技术能够识别与改变的生理和/或病理生理状态相关的分子变化的能力，在这种情况下，慢性OxS的状态提供了致癌的微环境。

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